{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T10:43:22Z","timestamp":1776077002331,"version":"3.50.1"},"reference-count":69,"publisher":"Bioscientifica","issue":"5","funder":[{"DOI":"10.13039\/100009863","name":"Neuroendocrine Tumor Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100009863","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005032","name":"Funda\u00e7\u00e3o Bial","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005032","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,3,10]]},"abstract":"<jats:p>The crosstalk between tumour cells and microenvironment components in pituitary neuroendocrine tumours (PitNETs), including chemokines, may impact tumour behaviour and clinical outcomes. CCL2 was previously identified as a key chemokine in PitNETs, but its role remains unknown. We aimed to study the role of CCL2 in defining the phenotype and clinical outcomes of PitNETs and in regulating macrophage chemotaxis, epithelial-to-mesenchymal transition (EMT) and angiogenesis. We studied CCL2 and E-cadherin expression, macrophages (CD68 and CD163) and vessels (CD31) in samples from 86 PitNET patients. Higher <jats:italic>CCL2<\/jats:italic> mRNA expression was found in patients who required multimodal and multiple treatments and had active disease at the last follow-up. Higher CCL2 immunoreactivity was observed in patients with larger PitNETs. Among somatotroph tumours, <jats:italic>CCL2<\/jats:italic> mRNA expression correlated with serum IGF-1 at the last follow-up. <jats:italic>CCL2<\/jats:italic> mRNA expression levels correlated negatively with <jats:italic>CDH1<\/jats:italic> expression and with E-cadherin complete membranous staining. <jats:italic>In vitro<\/jats:italic>, CCL2 downregulated E-cadherin expression in GH3 cells but did not affect cell morphology or migration. CCL2 expression correlated with the number of vessels, vessel perimeter and vessel area in PitNETs but not with PitNET-infiltrating macrophages. Our data suggest that CCL2 may lead to (or is at least a predictive marker of) poorer clinical outcomes and more difficult-to-treat PitNETs, potentially through its regulatory effects on different tumour-related mechanisms beyond immune cell chemotaxis, including in the activation of the EMT pathway and modulation of angiogenesis in PitNETs. Further studies are needed to corroborate our findings and to validate CCL2 as a potential predictive marker and therapeutic target in PitNETs.<\/jats:p>","DOI":"10.1530\/erc-24-0293","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T15:13:45Z","timestamp":1741619625000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":4,"title":["CCL2 expression predicts clinical outcomes and regulates E-cadherin and angiogenesis in pituitary tumours"],"prefix":"10.1530","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4839-8279","authenticated-orcid":true,"given":"Ana Lu\u00edsa","family":"Silva","sequence":"first","affiliation":[{"name":"Faculdade de Medicina, Universidade Cat\u00f3lica Portuguesa, Lisbon, Portugal"},{"name":"Instituto de Sa\u00fade Ambiental da Faculdade de Medicina da Universidade de Lisboa (ISAMB-FMUL), Lisbon, Portugal"}]},{"given":"Sayka","family":"Barry","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK"}]},{"given":"Mariana","family":"Lopes-Pinto","sequence":"additional","affiliation":[{"name":"Endocrinology Department, Hospital de Santa Maria, Unidade Local de Sa\u00fade de Santa Maria (ULSSM), Lisbon, Portugal"}]},{"given":"Rita","family":"Joaquim","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Lisbon University, Lisbon, Portugal"}]},{"given":"Catarina","family":"Miranda","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Lisbon University, Lisbon, Portugal"}]},{"given":"F\u00e1bio","family":"Reis","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Lisbon University, Lisbon, Portugal"}]},{"given":"Micaella","family":"Miranda","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Lisbon University, Lisbon, Portugal"}]},{"given":"Paulo","family":"Matos","sequence":"additional","affiliation":[{"name":"Human Genetics Department, Instituto Nacional de Sa\u00fade Doutor Ricardo Jorge, Lisbon, Portugal"},{"name":"BioISI \u2013 Instituto de Biossistemas e Ci\u00eancias Integrativas, Faculdade de Ci\u00eancias, Universidade de Lisboa, Lisbon, Portugal"}]},{"given":"Oniz","family":"Suleyman","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK"}]},{"given":"Tiago","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Pathology Department, Hospital de Santa Maria, Unidade Local de Sa\u00fade de Santa Maria (ULSSM), Lisbon, Portugal"}]},{"given":"Dolores","family":"L\u00f3pez-Presa","sequence":"additional","affiliation":[{"name":"Pathology Department, Hospital de Santa Maria, Unidade Local de Sa\u00fade de Santa Maria (ULSSM), Lisbon, Portugal"}]},{"given":"Gon\u00e7alo","family":"Borrecho","sequence":"additional","affiliation":[{"name":"Pathology Department, Unidade Local de Sa\u00fade Alentejo Central, \u00c9vora, Portugal"}]},{"given":"Francisco","family":"Tortosa","sequence":"additional","affiliation":[{"name":"Pituitary Tumor Unit, Pathology Department, Hospital CUF Descobertas, Lisbon, Portugal"}]},{"given":"Cla\u00fadia C","family":"Faria","sequence":"additional","affiliation":[{"name":"Neurosurgery Department, Hospital de Santa Maria, Unidade Local de Sa\u00fade de Santa Maria (ULSSM), Lisbon, Portugal"},{"name":"Cl\u00ednica Universit\u00e1ria de Neurocirurgia, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal"},{"name":"GIMM \u2013 Gulbenkian Institute for Molecular Medicine, Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4101-9432","authenticated-orcid":true,"given":"M\u00e1rta","family":"Korbonits","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4959-5725","authenticated-orcid":true,"given":"Pedro","family":"Marques","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina, Universidade Cat\u00f3lica Portuguesa, Lisbon, Portugal"},{"name":"Pituitary Tumor Unit, Endocrinology Department, Hospital CUF Descobertas, Lisbon, Portugal"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Cancer Res","first-page":"6080","article-title":"Obesity promotes breast cancer by CCL2-mediated macrophage recruitment and angiogenesis","volume":"73","author":"Arendt LM","year":"2013","unstructured":"Arendt LM\n, \nMccready J\n, \nKeller PJ\n, et al.\n 2013 Obesity promotes breast cancer by CCL2-mediated macrophage recruitment and angiogenesis. Cancer Res 73 6080\u20136093. (https:\/\/doi.org\/10.1158\/0008-5472.can-13-0926)"},{"key":"bib2","series-title":"J Pathol","first-page":"148","article-title":"The chemokine system and cancer","volume":"226","author":"Balkwill FR","year":"2012","unstructured":"Balkwill FR\n\n 2012 The chemokine system and cancer. J Pathol 226 148\u2013157. (https:\/\/doi.org\/10.1002\/path.3029)"},{"key":"bib3","series-title":"J Cell Sci","first-page":"5591","article-title":"The tumor microenvironment at a glance","volume":"125","author":"Balkwill FR","year":"2012","unstructured":"Balkwill FR\n, \nCapasso M\n & \nHagemann T\n\n 2012 The tumor microenvironment at a glance. J Cell Sci 125 5591\u20135596. (https:\/\/doi.org\/10.1242\/jcs.116392)"},{"key":"bib4","series-title":"Clin Cancer Res","first-page":"5022","article-title":"Overexpression of stromal cell-derived factor 1 and its receptor CXCR4 induces autocrine\/paracrine cell proliferation in human pituitary adenomas","volume":"14","author":"Barbieri F","year":"2008","unstructured":"Barbieri F\n, \nBajetto A\n, \nStumm R\n, et al.\n 2008 Overexpression of stromal cell-derived factor 1 and its receptor CXCR4 induces autocrine\/paracrine cell proliferation in human pituitary adenomas. Clin Cancer Res 14 5022\u20135032. (https:\/\/doi.org\/10.1158\/1078-0432.ccr-07-4717)"},{"key":"bib5","series-title":"Int J Endocrinol","article-title":"Emerging targets in pituitary adenomas: role of the CXCL12\/CXCR4-R7 system","volume":"2014","author":"Barbieri F","year":"2014","unstructured":"Barbieri F\n, \nThellung S\n, \nWurth R\n, et al.\n 2014 Emerging targets in pituitary adenomas: role of the CXCL12\/CXCR4-R7 system. Int J Endocrinol 2014 753524. (https:\/\/doi.org\/10.1155\/2014\/753524)"},{"key":"bib6","series-title":"Oncogene","first-page":"5381","article-title":"Tumor microenvironment defines the invasive phenotype of AIP-mutation-positive pituitary tumors","volume":"38","author":"Barry S","year":"2019","unstructured":"Barry S\n, \nCarlsen E\n, \nMarques P\n, et al.\n 2019 Tumor microenvironment defines the invasive phenotype of AIP-mutation-positive pituitary tumors. Oncogene 38 5381\u20135395. (https:\/\/doi.org\/10.1038\/s41388-019-0779-5)"},{"key":"bib7","series-title":"Nat Rev Cancer","first-page":"46","article-title":"Putting tumours in context","volume":"1","author":"Bissell MJ","year":"2001","unstructured":"Bissell MJ\n & \nRadisky D\n\n 2001 Putting tumours in context. Nat Rev Cancer 1 46\u201354. (https:\/\/doi.org\/10.1038\/35094059)"},{"key":"bib8","series-title":"J Clin Endocrinol Metab","first-page":"3662","article-title":"Growth hormone and the epithelial-to-mesenchymal transition","volume":"102","author":"Brittain AL","year":"2017","unstructured":"Brittain AL\n, \nBasu R\n, \nQian Y\n, et al.\n 2017 Growth hormone and the epithelial-to-mesenchymal transition. J Clin Endocrinol Metab 102 3662\u20133673. (https:\/\/doi.org\/10.1210\/jc.2017-01000)"},{"key":"bib9","series-title":"PLoS One","article-title":"Regulation of the CCL2 gene in pancreatic \u03b2-cells by IL-1\u03b2 and glucocorticoids: role of MKP-1","volume":"7","author":"Burke SJ","year":"2012","unstructured":"Burke SJ\n, \nGoff MR\n, \nUpdegraff BL\n, et al.\n 2012 Regulation of the CCL2 gene in pancreatic \u03b2-cells by IL-1\u03b2 and glucocorticoids: role of MKP-1. PLoS One 7 e46986. (https:\/\/doi.org\/10.1371\/journal.pone.0046986)"},{"key":"bib10","series-title":"Arch Endocrinol Metab","first-page":"568","article-title":"Growth hormone in the tumor microenvironment","volume":"63","author":"Chesnokova V","year":"2019","unstructured":"Chesnokova V\n & \nMelmed S\n\n 2019 Growth hormone in the tumor microenvironment. Arch Endocrinol Metab 63 568\u2013575. (https:\/\/doi.org\/10.20945\/2359-3997000000186)"},{"key":"bib11","series-title":"Int J Endocrinol","article-title":"Angiogenesis in pituitary adenomas: human studies and new mutant mouse models","volume":"2014","author":"Cristina C","year":"2014","unstructured":"Cristina C\n, \nLuque GM\n, \nDemarchi G\n, et al.\n 2014 Angiogenesis in pituitary adenomas: human studies and new mutant mouse models. Int J Endocrinol 2014 608497. (https:\/\/doi.org\/10.1155\/2014\/608497)"},{"key":"bib12","series-title":"Nat Rev Cancer","first-page":"97","article-title":"Regulatory networks defining EMT during cancer initiation and progression","volume":"13","author":"Craene BD","year":"2013","unstructured":"Craene BD\n & \nBerx G\n\n 2013 Regulatory networks defining EMT during cancer initiation and progression. Nat Rev Cancer 13 97\u2013110. (https:\/\/doi.org\/10.1038\/nrc3447)"},{"key":"bib13","series-title":"J Clin Endocrinol Metab","first-page":"1436","article-title":"Nuclear accumulation of e-cadherin correlates with loss of cytoplasmic membrane staining and invasion in pituitary adenomas","volume":"94","author":"Elston MS","year":"2009","unstructured":"Elston MS\n, \nGill AJ\n, \nConaglen JV\n, et al.\n 2009 Nuclear accumulation of e-cadherin correlates with loss of cytoplasmic membrane staining and invasion in pituitary adenomas. J Clin Endocrinol Metab 94 1436\u20131442. (https:\/\/doi.org\/10.1210\/jc.2008-2075)"},{"key":"bib14","series-title":"Front Immunol","article-title":"Targeting the CCL2\/CCR2 Axis in cancer immunotherapy: one stone, three birds?","volume":"12","author":"Fei L","year":"2021","unstructured":"Fei L\n, \nRen X\n, \nYu H\n, et al.\n 2021 Targeting the CCL2\/CCR2 Axis in cancer immunotherapy: one stone, three birds? Front Immunol 12 771210. (https:\/\/doi.org\/10.3389\/fimmu.2021.771210)"},{"key":"bib15","series-title":"Cell Death Dis","first-page":"421","article-title":"Glucocorticoid-induced leucine zipper regulates liver fibrosis by suppressing CCL2-mediated leukocyte recruitment","volume":"12","author":"Flamini S","year":"2021","unstructured":"Flamini S\n, \nSergeev P\n, \nViana DE Barros Z\n, et al.\n 2021 Glucocorticoid-induced leucine zipper regulates liver fibrosis by suppressing CCL2-mediated leukocyte recruitment. Cell Death Dis 12 421. (https:\/\/doi.org\/10.1038\/s41419-021-03704-w)"},{"key":"bib16","series-title":"Cell Tissue Res","first-page":"371","article-title":"Identification of M2 macrophages in anterior pituitary glands of normal rats and rats with estrogen-induced prolactinoma","volume":"368","author":"Fujiwara K","year":"2017","unstructured":"Fujiwara K\n, \nYatabe M\n, \nTofrizal A\n, et al.\n 2017 Identification of M2 macrophages in anterior pituitary glands of normal rats and rats with estrogen-induced prolactinoma. Cell Tissue Res 368 371\u2013378. (https:\/\/doi.org\/10.1007\/s00441-016-2564-x)"},{"key":"bib17","series-title":"Clin Endocrinol","first-page":"179","article-title":"Cytokine expression in human anterior pituitary adenomas","volume":"45","author":"Green VL","year":"1996","unstructured":"Green VL\n, \nAtkin SL\n, \nSpeirs V\n, et al.\n 1996 Cytokine expression in human anterior pituitary adenomas. Clin Endocrinol 45 179\u2013185. (https:\/\/doi.org\/10.1046\/j.1365-2265.1996.d01-1554.x)"},{"key":"bib18","series-title":"Front Endocrinol","first-page":"141","article-title":"Pituitary adenoma and the chemokine network: a systemic view","volume":"6","author":"Grizzi F","year":"2015","unstructured":"Grizzi F\n, \nBorroni EM\n, \nVacchini A\n, et al.\n 2015 Pituitary adenoma and the chemokine network: a systemic view. Front Endocrinol 6 141. (https:\/\/doi.org\/10.3389\/fendo.2015.00141)"},{"key":"bib19","series-title":"Endocr Relat Cancer","first-page":"701","article-title":"Somatostatin analogues in the control of neuroendocrine tumours: efficacy and mechanisms","volume":"15","author":"Grozinsky-Glasberg S","year":"2008","unstructured":"Grozinsky-Glasberg S\n, \nShimon I\n, \nKorbonits M\n, et al.\n 2008 Somatostatin analogues in the control of neuroendocrine tumours: efficacy and mechanisms. Endocr Relat Cancer 15 701\u2013720. (https:\/\/doi.org\/10.1677\/erc-07-0288)"},{"key":"bib20","series-title":"Cell Commun Signal","first-page":"82","article-title":"CCL2\/CCR2 signaling in cancer pathogenesis","volume":"18","author":"Hao Q","year":"2020","unstructured":"Hao Q\n, \nVadgama JV\n & \nWang P\n\n 2020 CCL2\/CCR2 signaling in cancer pathogenesis. Cell Commun Signal 18 82. (https:\/\/doi.org\/10.1186\/s12964-020-00589-8)"},{"key":"bib21","series-title":"PLoS One","article-title":"Dissecting the autocrine and paracrine roles of the CCR2-CCL2 axis in tumor survival and angiogenesis","volume":"7","author":"Izhak L","year":"2012","unstructured":"Izhak L\n, \nWildbaum G\n, \nJung S\n, et al.\n 2012 Dissecting the autocrine and paracrine roles of the CCR2-CCL2 axis in tumor survival and angiogenesis. PLoS One 7 e28305. (https:\/\/doi.org\/10.1371\/journal.pone.0028305)"},{"key":"bib22","series-title":"Front Oncol","article-title":"CCL2: an important mediator between tumor cells and host cells in tumor microenvironment","volume":"11","author":"Jin J","year":"2021","unstructured":"Jin J\n, \nLin J\n, \nXu A\n, et al.\n 2021 CCL2: an important mediator between tumor cells and host cells in tumor microenvironment. Front Oncol 11 722916. (https:\/\/doi.org\/10.3389\/fonc.2021.722916)"},{"key":"bib23","series-title":"Anticancer Res","first-page":"4497","article-title":"E-cadherin and angiopoietin-2 as potential biomarkers for colorectal cancer with peritoneal carcinomatosis","volume":"41","author":"Kim HK","year":"2021","unstructured":"Kim HK\n, \nYang Y\n, \nByeon S\n, et al.\n 2021 E-cadherin and angiopoietin-2 as potential biomarkers for colorectal cancer with peritoneal carcinomatosis. Anticancer Res 41 4497\u20134504. (https:\/\/doi.org\/10.21873\/anticanres.15260)"},{"key":"bib24","series-title":"Breast Cancer Res","first-page":"R217","article-title":"E-cadherin expression in primary carcinomas of the breast and its distant metastases","volume":"5","author":"Kowalski PJ","year":"2003","unstructured":"Kowalski PJ\n, \nRubin MA\n & \nKleer CG\n\n 2003 E-cadherin expression in primary carcinomas of the breast and its distant metastases. Breast Cancer Res 5 R217\u2013R222. (https:\/\/doi.org\/10.1186\/bcr651)"},{"key":"bib25","series-title":"Oncogene","first-page":"1316","article-title":"Glucocorticoids and histone deacetylase inhibitors cooperate to block the invasiveness of basal-like breast cancer cells through novel mechanisms","volume":"32","author":"Law ME","year":"2013","unstructured":"Law ME\n, \nCorsino PE\n, \nJahn SC\n, et al.\n 2013 Glucocorticoids and histone deacetylase inhibitors cooperate to block the invasiveness of basal-like breast cancer cells through novel mechanisms. Oncogene 32 1316\u20131329. (https:\/\/doi.org\/10.1038\/onc.2012.138)"},{"key":"bib28","series-title":"J Cell Biochem","first-page":"676","article-title":"CCR2 expression correlates with prostate cancer progression","volume":"101","author":"Lu Y","year":"2007","unstructured":"Lu Y\n, \nCai Z\n, \nXiao G\n, et al.\n 2007 CCR2 expression correlates with prostate cancer progression. J Cell Biochem 101 676\u2013685. (https:\/\/doi.org\/10.1002\/jcb.21220)"},{"key":"bib27","series-title":"Endocr Pathol","first-page":"263","article-title":"Immune cell infiltrates in pituitary adenomas: more macrophages in larger adenomas and more T cells in growth hormone adenomas","volume":"26","author":"Lu JQ","year":"2015","unstructured":"Lu JQ\n, \nAdam B\n, \nJack AS\n, et al.\n 2015 Immune cell infiltrates in pituitary adenomas: more macrophages in larger adenomas and more T cells in growth hormone adenomas. Endocr Pathol 26 263\u2013272. (https:\/\/doi.org\/10.1007\/s12022-015-9383-6)"},{"key":"bib26","series-title":"Atherosclerosis","article-title":"Sex-specific differences in cytokine signaling pathways in circulating monocytes of cardiovascular disease patients","volume":"384","author":"Lu C","year":"2023","unstructured":"Lu C\n, \nDonners M\n, \nKarel J\n, et al.\n 2023 Sex-specific differences in cytokine signaling pathways in circulating monocytes of cardiovascular disease patients. Atherosclerosis 384 117123. (https:\/\/doi.org\/10.1016\/j.atherosclerosis.2023.04.005)"},{"key":"bib29","series-title":"J Clin Endocrinol Metab","first-page":"289","article-title":"Tumor infiltrating lymphocytes but not serum pituitary antibodies are associated with poor clinical outcome after surgery in patients with pituitary adenoma","volume":"95","author":"Lupi I","year":"2010","unstructured":"Lupi I\n, \nManetti L\n, \nCaturegli P\n, et al.\n 2010 Tumor infiltrating lymphocytes but not serum pituitary antibodies are associated with poor clinical outcome after surgery in patients with pituitary adenoma. J Clin Endocrinol Metab 95 289\u2013296. (https:\/\/doi.org\/10.1210\/jc.2009-1583)"},{"key":"bib30","series-title":"Br J Cancer","first-page":"1117","article-title":"Single-cell sequencing of PIT1-positive pituitary adenoma highlights the pro-tumour microenvironment mediated by IFN-gamma-induced tumour-associated fibroblasts remodelling","volume":"128","author":"Lyu L","year":"2023","unstructured":"Lyu L\n, \nJiang Y\n, \nMa W\n, et al.\n 2023 Single-cell sequencing of PIT1-positive pituitary adenoma highlights the pro-tumour microenvironment mediated by IFN-gamma-induced tumour-associated fibroblasts remodelling. Br J Cancer 128 1117\u20131133. (https:\/\/doi.org\/10.1038\/s41416-022-02126-5)"},{"key":"bib31","series-title":"Cell Signal","article-title":"HSP47 contributes to angiogenesis by induction of CCL2 in bladder cancer","volume":"85","author":"Ma W","year":"2021","unstructured":"Ma W\n, \nOu T\n, \nCui X\n, et al.\n 2021 HSP47 contributes to angiogenesis by induction of CCL2 in bladder cancer. Cell Signal 85 110044. (https:\/\/doi.org\/10.1016\/j.cellsig.2021.110044)"},{"key":"bib34","series-title":"Trends Immunol","first-page":"549","article-title":"Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes","volume":"23","author":"Mantovani A","year":"2002","unstructured":"Mantovani A\n, \nSozzani S\n, \nLocati M\n, et al.\n 2002 Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol 23 549\u2013555. (https:\/\/doi.org\/10.1016\/s1471-4906(02)02302-5)"},{"key":"bib33","series-title":"Cancer Metastasis Rev","first-page":"315","article-title":"Role of tumor-associated macrophages in tumor progression and invasion","volume":"25","author":"Mantovani A","year":"2006","unstructured":"Mantovani A\n, \nSchioppa T\n, \nPorta C\n, et al.\n 2006 Role of tumor-associated macrophages in tumor progression and invasion. Cancer Metastasis Rev 25 315\u2013322. (https:\/\/doi.org\/10.1007\/s10555-006-9001-7)"},{"key":"bib32","series-title":"Cytokine Growth Factor Rev","first-page":"27","article-title":"The chemokine system in cancer biology and therapy","volume":"21","author":"Mantovani A","year":"2010","unstructured":"Mantovani A\n, \nSavino B\n, \nLocati M\n, et al.\n 2010 The chemokine system in cancer biology and therapy. Cytokine Growth Factor Rev 21 27\u201339. (https:\/\/doi.org\/10.1016\/j.cytogfr.2009.11.007)"},{"key":"bib39","series-title":"J Endocrinol Invest","first-page":"1047","article-title":"Tumour microenvironment and pituitary tumour behaviour","volume":"46","author":"Marques P","year":"2023","unstructured":"Marques P\n & \nKorbonits M\n\n 2023 Tumour microenvironment and pituitary tumour behaviour. J Endocrinol Invest 46 1047\u20131063. (https:\/\/doi.org\/10.1007\/s40618-023-02089-1)"},{"key":"bib35","series-title":"Acta Neuropathol Commun","first-page":"172","article-title":"Chemokines modulate the tumour microenvironment in pituitary neuroendocrine tumours","volume":"7","author":"Marques P","year":"2019a","unstructured":"Marques P\n, \nBarry S\n, \nCarlsen E\n, et al.\n 2019a Chemokines modulate the tumour microenvironment in pituitary neuroendocrine tumours. Acta Neuropathol Commun 7 172. (https:\/\/doi.org\/10.1186\/s40478-019-0830-3)"},{"key":"bib36","series-title":"Endocr Relat Cancer","first-page":"853","article-title":"Pituitary tumour fibroblast-derived cytokines influence tumour aggressiveness","volume":"26","author":"Marques P","year":"2019b","unstructured":"Marques P\n, \nBarry S\n, \nCarlsen E\n, et al.\n 2019b Pituitary tumour fibroblast-derived cytokines influence tumour aggressiveness. Endocr Relat Cancer 26 853\u2013865. (https:\/\/doi.org\/10.1530\/erc-19-0327)"},{"key":"bib37","series-title":"Endocrine","first-page":"593","article-title":"The role of the tumour microenvironment in the angiogenesis of pituitary tumours","volume":"70","author":"Marques P","year":"2020a","unstructured":"Marques P\n, \nBarry S\n, \nCarlsen E\n, et al.\n 2020a The role of the tumour microenvironment in the angiogenesis of pituitary tumours. Endocrine 70 593\u2013606. (https:\/\/doi.org\/10.1007\/s12020-020-02478-z)"},{"key":"bib38","series-title":"Front Neuroendocrinol","article-title":"The tumour microenvironment of pituitary neuroendocrine tumours","volume":"58","author":"Marques P","year":"2020b","unstructured":"Marques P\n, \nGrossman AB\n & \nKorbonits M\n\n 2020b The tumour microenvironment of pituitary neuroendocrine tumours. Front Neuroendocrinol 58 100852. (https:\/\/doi.org\/10.1016\/j.yfrne.2020.100852)"},{"key":"bib40","series-title":"Pituitary","first-page":"363","article-title":"The microenvironment of pituitary adenomas: biological, clinical and therapeutical implications","volume":"25","author":"Marques P","year":"2022","unstructured":"Marques P\n, \nSilva AL\n, \nLopez-Presa D\n, et al.\n 2022 The microenvironment of pituitary adenomas: biological, clinical and therapeutical implications. Pituitary 25 363\u2013382. (https:\/\/doi.org\/10.1007\/s11102-022-01211-5)"},{"key":"bib41","series-title":"Oncotarget","first-page":"76565","article-title":"Increased expression of programmed death ligand 1 (PD-L1) in human pituitary tumors","volume":"7","author":"Mei Y","year":"2016","unstructured":"Mei Y\n, \nBi WL\n, \nGreenwald NF\n, et al.\n 2016 Increased expression of programmed death ligand 1 (PD-L1) in human pituitary tumors. Oncotarget 7 76565\u201376576. (https:\/\/doi.org\/10.18632\/oncotarget.12088)"},{"key":"bib42","series-title":"Endocr Rev","first-page":"1003","article-title":"Clinical biology of the pituitary adenoma","volume":"43","author":"Melmed S","year":"2022","unstructured":"Melmed S\n, \nKaiser UB\n, \nLopes MB\n, et al.\n 2022 Clinical biology of the pituitary adenoma. Endocr Rev 43 1003\u20131037. (https:\/\/doi.org\/10.1210\/endrev\/bnac010)"},{"key":"bib43","series-title":"Int J Mol Sci","first-page":"10199","article-title":"Antiangiogenic effect of dopamine and dopaminergic agonists as an adjuvant therapeutic option in the treatment of cancer, endometriosis, and osteoarthritis","volume":"24","author":"Mendoza-Torreblanca JG","year":"2023","unstructured":"Mendoza-Torreblanca JG\n, \nCardenas-Rodriguez N\n, \nCarro-Rodriguez J\n, et al.\n 2023 Antiangiogenic effect of dopamine and dopaminergic agonists as an adjuvant therapeutic option in the treatment of cancer, endometriosis, and osteoarthritis. Int J Mol Sci 24 10199. (https:\/\/doi.org\/10.3390\/ijms241210199)"},{"key":"bib44","series-title":"Endocr Relat Cancer","first-page":"287","article-title":"The purine receptor P2X7R regulates the release of pro-inflammatory cytokines in human craniopharyngioma","volume":"24","author":"Nie J","year":"2017","unstructured":"Nie J\n, \nHuang GL\n, \nDeng SZ\n, et al.\n 2017 The purine receptor P2X7R regulates the release of pro-inflammatory cytokines in human craniopharyngioma. Endocr Relat Cancer 24 287\u2013296. (https:\/\/doi.org\/10.1530\/erc-16-0338)"},{"key":"bib45","series-title":"Front Physiol","first-page":"159","article-title":"Macrophages and chemokines as mediators of angiogenesis","volume":"4","author":"Owen JL","year":"2013","unstructured":"Owen JL\n & \nMohamadzadeh M\n\n 2013 Macrophages and chemokines as mediators of angiogenesis. Front Physiol 4 159. (https:\/\/doi.org\/10.3389\/fphys.2013.00159)"},{"key":"bib46","series-title":"Endocrine","first-page":"151","article-title":"Distribution of E- and N-cadherin in subgroups of non-functioning pituitary neuroendocrine tumours","volume":"77","author":"Oystese KAB","year":"2022","unstructured":"Oystese KAB\n, \nCasar-Borota O\n, \nBerg-Johnsen J\n, et al.\n 2022 Distribution of E- and N-cadherin in subgroups of non-functioning pituitary neuroendocrine tumours. Endocrine 77 151\u2013159. (https:\/\/doi.org\/10.1007\/s12020-022-03051-6)"},{"key":"bib47","series-title":"Sci Rep","first-page":"5420","article-title":"Metastasis-associated fibroblasts promote angiogenesis in metastasized pancreatic cancer via the CXCL8 and the CCL2 axes","volume":"10","author":"Pausch TM","year":"2020","unstructured":"Pausch TM\n, \nAue E\n, \nWirsik NM\n, et al.\n 2020 Metastasis-associated fibroblasts promote angiogenesis in metastasized pancreatic cancer via the CXCL8 and the CCL2 axes. Sci Rep 10 5420. (https:\/\/doi.org\/10.1038\/s41598-020-62416-x)"},{"key":"bib48","series-title":"Pituitary","first-page":"352","article-title":"Usefulness of a clinicopathological classification in predicting treatment-related outcomes and multimodal therapeutic approaches in pituitary adenoma patients: retrospective analysis on a Portuguese cohort of 129 patients from a tertiary pituitary center","volume":"26","author":"Peixe C","year":"2023","unstructured":"Peixe C\n, \nAlexandre MI\n, \nGomes AR\n, et al.\n 2023 Usefulness of a clinicopathological classification in predicting treatment-related outcomes and multimodal therapeutic approaches in pituitary adenoma patients: retrospective analysis on a Portuguese cohort of 129 patients from a tertiary pituitary center. Pituitary 26 352\u2013363. (https:\/\/doi.org\/10.1007\/s11102-023-01319-2)"},{"key":"bib49","series-title":"Hum Reprod","first-page":"850","article-title":"Use of dopamine agonists to target angiogenesis in women with endometriosis","volume":"36","author":"Pellicer N","year":"2021","unstructured":"Pellicer N\n, \nGalliano D\n, \nHerraiz S\n, et al.\n 2021 Use of dopamine agonists to target angiogenesis in women with endometriosis. Hum Reprod 36 850\u2013858. (https:\/\/doi.org\/10.1093\/humrep\/deaa337)"},{"key":"bib50","series-title":"Br J Cancer","first-page":"1835","article-title":"An immunohistochemically positive E-cadherin status is not always predictive for a good prognosis in human breast cancer","volume":"103","author":"Querzoli P","year":"2010","unstructured":"Querzoli P\n, \nCoradini D\n, \nPedriali M\n, et al.\n 2010 An immunohistochemically positive E-cadherin status is not always predictive for a good prognosis in human breast cancer. Br J Cancer 103 1835\u20131839. (https:\/\/doi.org\/10.1038\/sj.bjc.6605991)"},{"key":"bib51","series-title":"Front Physiol","first-page":"75","article-title":"Role of tumor associated macrophages in tumor angiogenesis and lymphangiogenesis","volume":"5","author":"Riabov V","year":"2014","unstructured":"Riabov V\n, \nGudima A\n, \nWang N\n, et al.\n 2014 Role of tumor associated macrophages in tumor angiogenesis and lymphangiogenesis. Front Physiol 5 75. (https:\/\/doi.org\/10.3389\/fphys.2014.00075)"},{"key":"bib52","series-title":"Nat Commun","first-page":"6889","article-title":"High endogenous CCL2 expression promotes the aggressive phenotype of human inflammatory breast cancer","volume":"12","author":"Rogic A","year":"2021","unstructured":"Rogic A\n, \nPant I\n, \nGrumolato L\n, et al.\n 2021 High endogenous CCL2 expression promotes the aggressive phenotype of human inflammatory breast cancer. Nat Commun 12 6889. (https:\/\/doi.org\/10.1038\/s41467-021-27108-8)"},{"key":"bib53","series-title":"Front Immunol","first-page":"1930","article-title":"Chemokine-induced macrophage polarization in inflammatory conditions","volume":"9","author":"Ruytinx P","year":"2018","unstructured":"Ruytinx P\n, \nProost P\n, \nVan Damme J\n, et al.\n 2018 Chemokine-induced macrophage polarization in inflammatory conditions. Front Immunol 9 1930. (https:\/\/doi.org\/10.3389\/fimmu.2018.01930)"},{"key":"bib54","series-title":"Cancer Chemother Pharmacol","first-page":"1041","article-title":"A first-in-human, first-in-class, phase I study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 in patients with solid tumors","volume":"71","author":"Sandhu SK","year":"2013","unstructured":"Sandhu SK\n, \nPapadopoulos K\n, \nFong PC\n, et al.\n 2013 A first-in-human, first-in-class, phase I study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 in patients with solid tumors. Cancer Chemother Pharmacol 71 1041\u20131050. (https:\/\/doi.org\/10.1007\/s00280-013-2099-8)"},{"key":"bib55","series-title":"Int J Mol Sci","first-page":"15719","article-title":"Aggressive PitNETs and potential target therapies: a systematic review of molecular and genetic pathways","volume":"24","author":"Serioli S","year":"2023","unstructured":"Serioli S\n, \nAgostini L\n, \nPietrantoni A\n, et al.\n 2023 Aggressive PitNETs and potential target therapies: a systematic review of molecular and genetic pathways. Int J Mol Sci 24 15719. (https:\/\/doi.org\/10.3390\/ijms242115719)"},{"key":"bib56","series-title":"N Am J Med Sci","first-page":"227","article-title":"E-cadherin as a diagnostic biomarker in breast cancer","volume":"3","author":"Singhai R","year":"2011","unstructured":"Singhai R\n, \nPatil VW\n, \nJaiswal SR\n, et al.\n 2011 E-cadherin as a diagnostic biomarker in breast cancer. N Am J Med Sci 3 227\u2013233. (https:\/\/doi.org\/10.4297\/najms.2011.3227)"},{"key":"bib57","series-title":"Eur J Endocrinol","first-page":"155","article-title":"IL-8 mRNA expression by in situ hybridisation in human pituitary adenomas","volume":"140","author":"Suliman ME","year":"1999","unstructured":"Suliman ME\n, \nRoyds JA\n, \nBaxter L\n, et al.\n 1999 IL-8 mRNA expression by in situ hybridisation in human pituitary adenomas. Eur J Endocrinol 140 155\u2013158. (https:\/\/doi.org\/10.1530\/eje.0.1400155)"},{"key":"bib58","series-title":"Ann Oncol","first-page":"1733","article-title":"Rationale for the use of somatostatin analogs as antitumor agents","volume":"17","author":"Susini C","year":"2006","unstructured":"Susini C\n & \nBuscail L\n\n 2006 Rationale for the use of somatostatin analogs as antitumor agents. Ann Oncol 17 1733\u20131742. (https:\/\/doi.org\/10.1093\/annonc\/mdl105)"},{"key":"bib59","series-title":"Cell Stress","first-page":"236","article-title":"New insights into the role of soluble E-cadherin in tumor angiogenesis","volume":"2","author":"Tang MKS","year":"2018","unstructured":"Tang MKS\n, \nIp PP\n & \nWong AST\n\n 2018 New insights into the role of soluble E-cadherin in tumor angiogenesis. Cell Stress 2 236\u2013238. (https:\/\/doi.org\/10.15698\/cst2018.09.154)"},{"key":"bib60","series-title":"Transl Cancer Res","first-page":"3129","article-title":"Glucocorticoid receptor regulates the epithelial-mesenchymal transition process through GR\/ZEB1\/E-cad and is involved in breast cancer endocrine drug resistance-a bioinformatics analysis","volume":"12","author":"Tang Y","year":"2023","unstructured":"Tang Y\n, \nMa J\n, \nZhang H\n, et al.\n 2023 Glucocorticoid receptor regulates the epithelial-mesenchymal transition process through GR\/ZEB1\/E-cad and is involved in breast cancer endocrine drug resistance-a bioinformatics analysis. Transl Cancer Res 12 3129\u20133146. (https:\/\/doi.org\/10.21037\/tcr-23-1628)"},{"key":"bib61","series-title":"Cell","first-page":"871","article-title":"Epithelial-mesenchymal transitions in development and disease","volume":"139","author":"Thiery JP","year":"2009","unstructured":"Thiery JP\n, \nAcloque H\n, \nHuang RY\n, et al.\n 2009 Epithelial-mesenchymal transitions in development and disease. Cell 139 871\u2013890. (https:\/\/doi.org\/10.1016\/j.cell.2009.11.007)"},{"key":"bib62","series-title":"Front Endocrinol","article-title":"Monocyte trafficking and polarization contribute to sex differences in meta-inflammation","volume":"13","author":"Varghese M","year":"2022","unstructured":"Varghese M\n, \nClemente J\n, \nLerner A\n, et al.\n 2022 Monocyte trafficking and polarization contribute to sex differences in meta-inflammation. Front Endocrinol 13 826320. (https:\/\/doi.org\/10.3389\/fendo.2022.826320)"},{"key":"bib63","series-title":"Growth Horm IGF Res","first-page":"134","article-title":"Interleukin-8 production from human somatotroph adenoma cells is stimulated by interleukin-1beta and inhibited by growth hormone releasing hormone and somatostatin","volume":"21","author":"Vindelov SD","year":"2011","unstructured":"Vindelov SD\n, \nHartoft-Nielsen ML\n, \nRasmussen AK\n, et al.\n 2011 Interleukin-8 production from human somatotroph adenoma cells is stimulated by interleukin-1beta and inhibited by growth hormone releasing hormone and somatostatin. Growth Horm IGF Res 21 134\u2013139. (https:\/\/doi.org\/10.1016\/j.ghir.2011.03.005)"},{"key":"bib64","series-title":"J Neuro Oncol","first-page":"89","article-title":"The expression profile of PD-L1 and CD8(+) lymphocyte in pituitary adenomas indicating for immunotherapy","volume":"139","author":"Wang PF","year":"2018","unstructured":"Wang PF\n, \nWang TJ\n, \nYang YK\n, et al.\n 2018 The expression profile of PD-L1 and CD8(+) lymphocyte in pituitary adenomas indicating for immunotherapy. J Neuro Oncol 139 89\u201395. (https:\/\/doi.org\/10.1007\/s11060-018-2844-2)"},{"key":"bib65","series-title":"Cell Death Dis","first-page":"781","article-title":"CCL2 promotes macrophages-associated chemoresistance via MCPIP1 dual catalytic activities in multiple myeloma","volume":"10","author":"Xu R","year":"2019","unstructured":"Xu R\n, \nLi Y\n, \nYan H\n, et al.\n 2019 CCL2 promotes macrophages-associated chemoresistance via MCPIP1 dual catalytic activities in multiple myeloma. Cell Death Dis 10 781. (https:\/\/doi.org\/10.1038\/s41419-019-2012-4)"},{"key":"bib66","series-title":"Oncotarget","first-page":"2212","article-title":"Stratifying nonfunctional pituitary adenomas into two groups distinguished by macrophage subtypes","volume":"10","author":"Yagnik G","year":"2019","unstructured":"Yagnik G\n, \nRutowski MJ\n, \nShah SS\n, et al.\n 2019 Stratifying nonfunctional pituitary adenomas into two groups distinguished by macrophage subtypes. Oncotarget 10 2212\u20132223. (https:\/\/doi.org\/10.18632\/oncotarget.26775)"},{"key":"bib67","series-title":"Thyroid","first-page":"1347","article-title":"The role of chemokines in thyroid carcinoma","volume":"27","author":"Yapa S","year":"2017","unstructured":"Yapa S\n, \nMulla O\n, \nGreen V\n, et al.\n 2017 The role of chemokines in thyroid carcinoma. Thyroid 27 1347\u20131359. (https:\/\/doi.org\/10.1089\/thy.2016.0660)"},{"key":"bib68","series-title":"Cytokine","first-page":"71","article-title":"The production of monocyte chemoattractant protein-1 (MCP-1)\/CCL2 in tumor microenvironments","volume":"98","author":"Yoshimura T","year":"2017","unstructured":"Yoshimura T\n\n 2017 The production of monocyte chemoattractant protein-1 (MCP-1)\/CCL2 in tumor microenvironments. Cytokine 98 71\u201378. (https:\/\/doi.org\/10.1016\/j.cyto.2017.02.001)"},{"key":"bib69","series-title":"Front Oncol","first-page":"989","article-title":"Cadherin signaling in cancer: its functions and role as a therapeutic target","volume":"9","author":"Yu W","year":"2019","unstructured":"Yu W\n, \nYang L\n, \nLi T\n, et al.\n 2019 Cadherin signaling in cancer: its functions and role as a therapeutic target. Front Oncol 9 989. (https:\/\/doi.org\/10.3389\/fonc.2019.00989)"}],"container-title":["Endocrine-Related Cancer"],"original-title":[],"link":[{"URL":"https:\/\/erc.bioscientifica.com\/view\/journals\/erc\/32\/5\/ERC-24-0293.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/erc.bioscientifica.com\/downloadpdf\/journals\/erc\/32\/5\/ERC-24-0293.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/erc.bioscientifica.com\/downloadpdf\/journals\/erc\/32\/5\/ERC-24-0293.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T22:20:28Z","timestamp":1745878828000},"score":1,"resource":{"primary":{"URL":"https:\/\/erc.bioscientifica.com\/view\/journals\/erc\/32\/5\/ERC-24-0293.xml"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,10]]},"references-count":69,"journal-issue":{"issue":"5"},"URL":"https:\/\/doi.org\/10.1530\/erc-24-0293","relation":{},"ISSN":["1351-0088","1479-6821"],"issn-type":[{"value":"1351-0088","type":"print"},{"value":"1479-6821","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,10]]}}}