{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:19:47Z","timestamp":1790684387511,"version":"4.1.0"},"reference-count":73,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T00:00:00Z","timestamp":1673568000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T00:00:00Z","timestamp":1673568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Construction of Key Disciplines of Tongji Hospital in the Fifth Cycle","award":["ZD16-FC-1"],"award-info":[{"award-number":["ZD16-FC-1"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81802583"],"award-info":[{"award-number":["81802583"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071630"],"award-info":[{"award-number":["82071630"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771560"],"award-info":[{"award-number":["81771560"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Discov Onc"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Objectives<\/jats:title>\n                <jats:p>To explore the correlation between tumor endothelial marker 1 (TEM1) and matrix metalloproteinase 2 (MMP-2) in uterine sarcoma and their roles in the progression of uterine sarcoma.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Uterine leiomyosarcoma (uLMS, n\u2009=\u200925) and uterine leiomyoma (n\u2009=\u200925) specimens were collected from a total of 50 patients. Immunohistochemistry assay was conducted to determine the expression of TEM1, MMP-2 and MMP-9. TEM1 over expression (hTEM1) and low expression (shRNA-TEM1) MES-SA cell lines were established as in vitro uterine sarcoma models. MMP-2 mRNA, protein expression and enzymatic activity were verified using qPCR, Western blot and gelatin zymography respectively. MMP-2 expression was downregulated using MMP-2 siRNA in hTEM1 MES-SA cells to better study the role of MMP-2. The invasive and migratory capacities of hTEM1, shRNA-TEM1, and hTEM1 treated with MMP-2 siRNA MES-SA cells were determined using transwell assays. Extracellular matrix (ECM) remodeling mediated by TEM1 was examined using cell-ECM adhesion and fluorescent gelatin-ECM degradation assays. The\u00a0immunofluorescence of F-actin was examined to analyze the formation of invadopodia. Subcutaneous and intraperitoneal xenografts were established to validate the role of TEM1 in promoting uterine sarcoma metastasis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>TEM1 and MMP-2 were expressed in 92% (n\u2009=\u200923) and 88% (n\u2009=\u200922) of uterine leiomyosarcoma specimens, respectively. Both TEM1 and MMP-2 were highly expressed in 100% (n\u2009=\u200917) of high stage (III-IV) uterine leiomyosarcoma specimens. In addition, TEM1 expression was positively correlated with MMP-2 expression in uterine leiomyosarcoma. The successful establishment of in vitro uterine sarcoma models was confirmed with qPCR and Western blotting tests. TEM1 promoted the invasion and metastasis of uterine sarcoma in vivo and in vitro. MMP-2 expression and activity were up-regulated in hTEM1 cells but down-regulated in shRNA-TEM1 cells. Importantly, MMP-2 knockdown impaired the invasive and migratory capacity of hTEM1 cells. TEM1 promoted ECM remodeling by increasing cell-ECM adhesion and ECM degradation. TEM1 overexpression also induced the formation of invadopodia.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>TEM1 was co-expressed and positively correlated with MMP-2 in uterine leiomyosarcoma specimens. In addition, both TEM1 and MMP-2 were associated with tumor development. TEM1 promoted uterine sarcoma progression by regulating MMP-2 activity and ECM remodeling.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s12672-023-00613-6","type":"journal-article","created":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T18:03:13Z","timestamp":1673632993000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["TEM1 up-regulates MMP-2 and promotes ECM remodeling for facilitating invasion and migration of uterine sarcoma"],"prefix":"10.1007","volume":"14","author":[{"given":"Chenghao","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhuizi","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongsheng","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaifang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowen","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,1,13]]},"reference":[{"issue":"11","key":"613_CR1","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1159\/000494393","volume":"41","author":"P Mallmann","year":"2018","unstructured":"Mallmann P. Uterine sarcoma\u2014difficult to diagnose, hard to treat. Oncol Res Treat. 2018;41(11):674.","journal-title":"Oncol Res Treat"},{"issue":"6","key":"613_CR2","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1097\/IGC.0000000000000720","volume":"26","author":"M Hosh","year":"2016","unstructured":"Hosh M, Antar S, Nazzal A, Warda M, Gibreel A, Refky B. Uterine sarcoma: analysis of 13,089 cases based on surveillance, epidemiology, and end results database. Int J Gynecol Cancer. 2016;26(6):1098\u2013104.","journal-title":"Int J Gynecol Cancer"},{"issue":"3","key":"613_CR3","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1111\/j.1365-2559.2009.03231.x","volume":"54","author":"VM Abeler","year":"2009","unstructured":"Abeler VM, Royne O, Thoresen S, Danielsen HE, Nesland JM, Kristensen GB. Uterine sarcomas in Norway. a histopathological and prognostic survey of a total population from 1970 to 2000 including 419 patients. Histopathology. 2009;54(3):355\u201364.","journal-title":"Histopathology"},{"issue":"3","key":"613_CR4","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/j.mvr.2008.07.008","volume":"76","author":"RG Bagley","year":"2008","unstructured":"Bagley RG, Honma N, Weber W, Boutin P, Rouleau C, Shankara S, et al. Endosialin\/TEM 1\/CD248 is a pericyte marker of embryonic and tumor neovascularization. Microvasc Res. 2008;76(3):180\u20138.","journal-title":"Microvasc Res"},{"issue":"18","key":"613_CR5","doi-asserted-by":"publisher","first-page":"3892","DOI":"10.1158\/0008-5472.CAN-19-2691","volume":"80","author":"F Yang","year":"2020","unstructured":"Yang F, Wei Y, Han D, Li Y, Shi S, Jiao D, et al. Interaction with CD68 and regulation of GAS6 expression by Endosialin in fibroblasts drives recruitment and polarization of macrophages in hepatocellular carcinoma. Cancer Res. 2020;80(18):3892\u2013905.","journal-title":"Cancer Res"},{"issue":"46","key":"613_CR6","doi-asserted-by":"publisher","first-page":"17965","DOI":"10.1073\/pnas.0705647104","volume":"104","author":"B Tomkowicz","year":"2007","unstructured":"Tomkowicz B, Rybinski K, Foley B, Ebel W, Kline B, Routhier E, et al. Interaction of endosialin\/TEM1 with extracellular matrix proteins mediates cell adhesion and migration. Proc Natl Acad Sci U S A. 2007;104(46):17965\u201370.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"9","key":"613_CR7","doi-asserted-by":"publisher","first-page":"2081","DOI":"10.1158\/1535-7163.MCT-15-0312","volume":"14","author":"C Rouleau","year":"2015","unstructured":"Rouleau C, Gianolio DA, Smale R, Roth SD, Krumbholz R, Harper J, et al. Anti-endosialin antibody-drug conjugate: potential in sarcoma and other malignancies. Mol Cancer Ther. 2015;14(9):2081\u20139.","journal-title":"Mol Cancer Ther"},{"key":"613_CR8","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1186\/1471-2407-9-417","volume":"9","author":"EB Carson-Walter","year":"2009","unstructured":"Carson-Walter EB, Winans BN, Whiteman MC, Liu Y, Jarvela S, Haapasalo H, et al. Characterization of TEM1\/endosialin in human and murine brain tumors. BMC Cancer. 2009;9:417.","journal-title":"BMC Cancer"},{"issue":"2","key":"613_CR9","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1007\/s12307-015-0168-8","volume":"8","author":"E Kiyohara","year":"2015","unstructured":"Kiyohara E, Donovan N, Takeshima L, Huang S, Wilmott JS, Scolyer RA, et al. Endosialin expression in metastatic melanoma tumor microenvironment vasculature: potential therapeutic implications. Cancer Microenviron. 2015;8(2):111\u20138.","journal-title":"Cancer Microenviron"},{"issue":"1","key":"613_CR10","first-page":"65","volume":"12","author":"EI Matthaiou","year":"2022","unstructured":"Matthaiou EI, Guo Y, Barar J, Sandaltzopoulos R, Kandalaft LE, Li C, et al. TEM1-targeting PEGylated PLGA shikonin nanoformulation for immunomodulation and eradication of ovarian cancer. Bioimpacts. 2022;12(1):65\u201386.","journal-title":"Bioimpacts"},{"issue":"5","key":"613_CR11","doi-asserted-by":"publisher","first-page":"e26944","DOI":"10.1002\/pbc.26944","volume":"65","author":"RE Norris","year":"2018","unstructured":"Norris RE, Fox E, Reid JM, Ralya A, Liu XW, Minard C, et al. Phase 1 trial of Ontuxizumab (MORAb-004) in children with relapsed or refractory solid tumors: a report from the children\u2019s oncology group phase 1 pilot consortium (ADVL1213). Pediatr Blood Cancer. 2018;65(5):e26944.","journal-title":"Pediatr Blood Cancer"},{"issue":"14","key":"613_CR12","doi-asserted-by":"publisher","first-page":"2445","DOI":"10.1002\/cncr.32084","volume":"125","author":"RL Jones","year":"2019","unstructured":"Jones RL, Chawla SP, Attia S, Schoffski P, Gelderblom H, Chmielowski B, et al. A phase 1 and randomized controlled phase 2 trial of the safety and efficacy of the combination of gemcitabine and docetaxel with ontuxizumab (MORAb-004) in metastatic soft-tissue sarcomas. Cancer. 2019;125(14):2445\u201354.","journal-title":"Cancer"},{"issue":"6","key":"613_CR13","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.1158\/1078-0432.CCR-14-1829","volume":"21","author":"LA Diaz Jr","year":"2015","unstructured":"Diaz LA Jr, Coughlin CM, Weil SC, Fishel J, Gounder MM, Lawrence S, et al. A first-in-human phase I study of MORAb-004, a monoclonal antibody to endosialin in patients with advanced solid tumors. Clin Cancer Res. 2015;21(6):1281\u20138.","journal-title":"Clin Cancer Res"},{"issue":"2","key":"613_CR14","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1158\/1078-0432.CCR-17-1558","volume":"24","author":"A Grothey","year":"2018","unstructured":"Grothey A, Strosberg JR, Renfro LA, Hurwitz HI, Marshall JL, Safran H, et al. A randomized, double-blind, placebo-controlled phase II study of the efficacy and safety of monotherapy Ontuxizumab (MORAb-004) plus best supportive care in patients with chemorefractory metastatic colorectal cancer. Clin Cancer Res. 2018;24(2):316\u201325.","journal-title":"Clin Cancer Res"},{"key":"613_CR15","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.ejca.2017.10.035","volume":"90","author":"Y Guo","year":"2018","unstructured":"Guo Y, Hu J, Wang Y, Peng X, Min J, Wang J, et al. Tumour endothelial marker 1\/endosialin-mediated targeting of human sarcoma. Eur J Cancer. 2018;90:111\u201321.","journal-title":"Eur J Cancer"},{"issue":"12","key":"613_CR16","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1038\/nrm3904","volume":"15","author":"C Bonnans","year":"2014","unstructured":"Bonnans C, Chou J, Werb Z. Remodelling the extracellular matrix in development and disease. Nat Rev Mol Cell Biol. 2014;15(12):786\u2013801.","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"1","key":"613_CR17","doi-asserted-by":"publisher","first-page":"5120","DOI":"10.1038\/s41467-020-18794-x","volume":"11","author":"J Winkler","year":"2020","unstructured":"Winkler J, Abisoye-Ogunniyan A, Metcalf KJ, Werb Z. Concepts of extracellular matrix remodelling in tumour progression and metastasis. Nat Commun. 2020;11(1):5120.","journal-title":"Nat Commun"},{"issue":"2","key":"613_CR18","first-page":"183","volume":"63","author":"S Kontsekova","year":"2016","unstructured":"Kontsekova S, Polcicova K, Takacova M, Pastorekova S. Endosialin: molecular and functional links to tumor angiogenesis. Neoplasma. 2016;63(2):183\u201392.","journal-title":"Neoplasma"},{"key":"613_CR19","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1186\/1471-2407-11-162","volume":"11","author":"M Maia","year":"2011","unstructured":"Maia M, DeVriese A, Janssens T, Moons M, Lories RJ, Tavernier J, et al. CD248 facilitates tumor growth via its cytoplasmic domain. BMC Cancer. 2011;11:162.","journal-title":"BMC Cancer"},{"issue":"4","key":"613_CR20","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1083\/jcb.201102147","volume":"196","author":"P Lu","year":"2012","unstructured":"Lu P, Weaver VM, Werb Z. The extracellular matrix: a dynamic niche in cancer progression. J Cell Biol. 2012;196(4):395\u2013406.","journal-title":"J Cell Biol"},{"issue":"23","key":"613_CR21","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.21037\/atm-21-6271","volume":"9","author":"S Liu","year":"2021","unstructured":"Liu S, Xu C, Zhang K, Han D, Yang F, Li Y, et al. CD248 as a bridge between angiogenesis and immunosuppression: a promising prognostic and therapeutic target for renal cell carcinoma. Ann Transl Med. 2021;9(23):1741.","journal-title":"Ann Transl Med"},{"issue":"9","key":"613_CR22","doi-asserted-by":"publisher","first-page":"e107146","DOI":"10.1371\/journal.pone.0107146","volume":"9","author":"AJ Naylor","year":"2014","unstructured":"Naylor AJ, McGettrick HM, Maynard WD, May P, Barone F, Croft AP, et al. A differential role for CD248 (Endosialin) in PDGF-mediated skeletal muscle angiogenesis. PLoS ONE. 2014;9(9):e107146.","journal-title":"PLoS ONE"},{"issue":"2","key":"613_CR23","first-page":"1488","volume":"20","author":"P Di Benedetto","year":"2019","unstructured":"Di Benedetto P, Ruscitti P, Liakouli V, Del Galdo F, Giacomelli R, Cipriani P. Linking myofibroblast generation and microvascular alteration: the role of CD248 from pathogenesis to therapeutic target (Review). Mol Med Rep. 2019;20(2):1488\u201398.","journal-title":"Mol Med Rep"},{"issue":"3","key":"613_CR24","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.ijgo.2008.12.008","volume":"104","author":"J Prat","year":"2009","unstructured":"Prat J. FIGO staging for uterine sarcomas. Int J Gynaecol Obstet. 2009;104(3):177\u20138.","journal-title":"Int J Gynaecol Obstet"},{"issue":"3","key":"613_CR25","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/j.pathol.2020.01.436","volume":"52","author":"Y Jin","year":"2020","unstructured":"Jin Y, Liang ZY, Zhou WX, Zhou L. High MMP14 expression is predictive of poor prognosis in resectable hepatocellular carcinoma. Pathology. 2020;52(3):359\u201365.","journal-title":"Pathology"},{"key":"613_CR26","doi-asserted-by":"publisher","DOI":"10.1016\/j.pathol.2020.01.190","author":"T Fielder","year":"2021","unstructured":"Fielder T, Butler J, Tierney G, Holmes M, Lam KY, Satgunaseelan L, et al. ROS1 rearrangements in lung adenocarcinomas are defined by diffuse strong immunohistochemical expression of ROS1. Pathology. 2021. https:\/\/doi.org\/10.1016\/j.pathol.2020.01.190.","journal-title":"Pathology"},{"issue":"1","key":"613_CR27","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1093\/ajcp\/aqaa118","volume":"155","author":"S De Michele","year":"2021","unstructured":"De Michele S, Remotti HE, Del Portillo A, Lagana SM, Szabolcs M, Saqi A. SATB2 in neoplasms of lung, pancreatobiliary, and gastrointestinal origins. Am J Clin Pathol. 2021;155(1):124\u201332.","journal-title":"Am J Clin Pathol"},{"key":"613_CR28","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.lungcan.2021.08.003","volume":"160","author":"CC Cheung","year":"2021","unstructured":"Cheung CC, Smith AC, Albadine R, Bigras G, Bojarski A, Couture C, et al. Canadian ROS proto-oncogene 1 study (CROS) for multi-institutional implementation of ROS1 testing in non-small cell lung cancer. Lung Cancer. 2021;160:127\u201335.","journal-title":"Lung Cancer"},{"issue":"16","key":"613_CR29","doi-asserted-by":"publisher","first-page":"2040","DOI":"10.1016\/S0959-8049(01)00235-0","volume":"37","author":"B Davidson","year":"2001","unstructured":"Davidson B, Reich R, Berner A, Givant-Horwitz V, Goldberg I, Risberg B, et al. Ovarian carcinoma cells in serous effusions show altered MMP-2 and TIMP-2 mRNA levels. Eur J Cancer. 2001;37(16):2040\u20139.","journal-title":"Eur J Cancer"},{"key":"613_CR30","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1007\/978-1-59745-413-1_15","volume":"522","author":"VV Artym","year":"2009","unstructured":"Artym VV, Yamada KM, Mueller SC. ECM degradation assays for analyzing local cell invasion. Methods Mol Biol. 2009;522:211\u20139.","journal-title":"Methods Mol Biol"},{"issue":"1","key":"613_CR31","first-page":"73","volume":"39","author":"C Rouleau","year":"2011","unstructured":"Rouleau C, Smale R, Fu YS, Hui G, Wang F, Hutto E, et al. Endosialin is expressed in high grade and advanced sarcomas: evidence from clinical specimens and preclinical modeling. Int J Oncol. 2011;39(1):73\u201389.","journal-title":"Int J Oncol"},{"issue":"31","key":"613_CR32","doi-asserted-by":"publisher","first-page":"5787","DOI":"10.3748\/wjg.v23.i31.5787","volume":"23","author":"Y Xie","year":"2017","unstructured":"Xie Y, Lin JZ, Wang AQ, Xu WY, Long JY, Luo YF, et al. Threonine and tyrosine kinase may serve as a prognostic biomarker for gallbladder cancer. World J Gastroenterol. 2017;23(31):5787\u201397.","journal-title":"World J Gastroenterol"},{"issue":"3\u20134","key":"613_CR33","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1155\/2001\/418547","volume":"23","author":"B Davidson","year":"2001","unstructured":"Davidson B. Ovarian carcinoma and serous effusions Changing views regarding tumor progression and review of current literature. Anal Cell Pathol. 2001;23(3\u20134):107\u201328.","journal-title":"Anal Cell Pathol"},{"issue":"9","key":"613_CR34","first-page":"13133","volume":"10","author":"Y Guo","year":"2017","unstructured":"Guo Y, Chen KW, Zhang Y, Guo S, Wang JJ, Chu L, et al. TEM1 knock-down inhibits the proliferation and metastasis of MES-SA uterine sarcoma cells. Int J Clin Exp Med. 2017;10(9):13133\u201342.","journal-title":"Int J Clin Exp Med"},{"key":"613_CR35","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1007\/978-1-59745-413-1_14","volume":"522","author":"MJ Humphries","year":"2009","unstructured":"Humphries MJ. Cell adhesion assays. Methods Mol Biol. 2009;522:203\u201310.","journal-title":"Methods Mol Biol"},{"issue":"19","key":"613_CR36","doi-asserted-by":"publisher","first-page":"32270","DOI":"10.18632\/oncotarget.15650","volume":"8","author":"Z Aktary","year":"2017","unstructured":"Aktary Z, Alaee M, Pasdar M. Beyond cell-cell adhesion: Plakoglobin and the regulation of tumorigenesis and metastasis. Oncotarget. 2017;8(19):32270\u201391.","journal-title":"Oncotarget"},{"issue":"9","key":"613_CR37","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1038\/s41568-018-0038-z","volume":"18","author":"H Hamidi","year":"2018","unstructured":"Hamidi H, Ivaska J. Every step of the way: integrins in cancer progression and metastasis. Nat Rev Cancer. 2018;18(9):533\u201348.","journal-title":"Nat Rev Cancer"},{"key":"613_CR38","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1007\/978-1-0716-1350-4_11","volume":"2294","author":"R Fontana","year":"2021","unstructured":"Fontana R, Yang J. Matrix degradation assay to measure the ability of tumor cells to degrade extracellular matrix. Methods Mol Biol. 2021;2294:151\u201363.","journal-title":"Methods Mol Biol"},{"issue":"1","key":"613_CR39","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s12964-021-00710-5","volume":"19","author":"RAC Machado","year":"2021","unstructured":"Machado RAC, Stojevski D, De Landtsheer S, Lucarelli P, Baron A, Sauter T, et al. L-plastin Ser5 phosphorylation is modulated by the PI3K\/SGK pathway and promotes breast cancer cell invasiveness. Cell Commun Signal. 2021;19(1):22.","journal-title":"Cell Commun Signal"},{"issue":"Pt 20","key":"613_CR40","first-page":"4707","volume":"126","author":"R Albrechtsen","year":"2013","unstructured":"Albrechtsen R, Kveiborg M, Stautz D, Vikes\u00e5 J, Noer JB, Kotzsh A, et al. ADAM12 redistributes and activates MMP-14, resulting in gelatin degradation, reduced apoptosis and increased tumor growth. J Cell Sci. 2013;126(Pt 20):4707\u201320.","journal-title":"J Cell Sci"},{"key":"613_CR41","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1007\/978-1-0716-1205-7_3","volume":"2265","author":"E Mazurkiewicz","year":"2021","unstructured":"Mazurkiewicz E, Mr\u00f3wczy\u0144ska E, Simiczyjew A, Nowak D, Mazur AJ. A fluorescent gelatin degradation assay to study melanoma breakdown of extracellular matrix. Methods Mol Biol. 2021;2265:47\u201363.","journal-title":"Methods Mol Biol"},{"issue":"20","key":"613_CR42","doi-asserted-by":"publisher","first-page":"13856","DOI":"10.1074\/jbc.M709401200","volume":"283","author":"B Desai","year":"2008","unstructured":"Desai B, Ma T, Chellaiah MA. Invadopodia and matrix degradation, a new property of prostate cancer cells during migration and invasion. J Biol Chem. 2008;283(20):13856\u201366.","journal-title":"J Biol Chem"},{"key":"613_CR43","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201907058","author":"N Pacheco-Fernandez","year":"2020","unstructured":"Pacheco-Fernandez N, Pakdel M, Blank B, Sanchez-Gonzalez I, Weber K, Tran ML, et al. Nucleobindin-1 regulates ECM degradation by promoting intra-Golgi trafficking of MMPs. J Cell Biol. 2020. https:\/\/doi.org\/10.1083\/jcb.201907058.","journal-title":"J Cell Biol"},{"issue":"4","key":"613_CR44","first-page":"841","volume":"39","author":"C Rouleau","year":"2011","unstructured":"Rouleau C, Smale R, Sancho J, Fu YS, Kurtzberg L, Weber W, et al. Endosialin: a novel malignant cell therapeutic target for neuroblastoma. Int J Oncol. 2011;39(4):841\u201351.","journal-title":"Int J Oncol"},{"issue":"36","key":"613_CR45","doi-asserted-by":"publisher","first-page":"60368","DOI":"10.18632\/oncotarget.19499","volume":"8","author":"E Capone","year":"2017","unstructured":"Capone E, Piccolo E, Fichera I, Ciufici P, Barcaroli D, Sala A, et al. Generation of a novel antibody-drug conjugate targeting endosialin: potent and durable antitumor response in sarcoma. Oncotarget. 2017;8(36):60368\u201377.","journal-title":"Oncotarget"},{"issue":"2","key":"613_CR46","doi-asserted-by":"publisher","first-page":"42","DOI":"10.3892\/ol.2021.13160","volume":"23","author":"Y Kondo","year":"2022","unstructured":"Kondo Y, Honoki K, Kishi S, Mori S, Fujiwara-Tani R, Tsukamoto S, et al. Endosialin\/CD248 may be a potential therapeutic target to prevent the invasion and metastasis in osteosarcoma. Oncol Lett. 2022;23(2):42.","journal-title":"Oncol Lett"},{"issue":"4","key":"613_CR47","doi-asserted-by":"publisher","first-page":"443","DOI":"10.4055\/cios.2014.6.4.443","volume":"6","author":"HK Yang","year":"2014","unstructured":"Yang HK, Jeong KC, Kim YK, Jung ST. Role of matrix metalloproteinase (MMP) 2 and MMP-9 in soft tissue sarcoma. Clin Orthop Surg. 2014;6(4):443\u201354.","journal-title":"Clin Orthop Surg"},{"issue":"5","key":"613_CR48","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1016\/j.bjorl.2019.10.009","volume":"87","author":"Z Song","year":"2021","unstructured":"Song Z, Wang J, Su Q, Luan M, Chen X, Xu X. The role of MMP-2 and MMP-9 in the metastasis and development of hypopharyngeal carcinoma. Braz J Otorhinolaryngol. 2021;87(5):521\u20138.","journal-title":"Braz J Otorhinolaryngol"},{"issue":"2","key":"613_CR49","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1007\/s11033-019-05216-5","volume":"47","author":"AA Alrehaili","year":"2020","unstructured":"Alrehaili AA, Gharib AF, Karam RA, Alhakami RA, El Sawy WH, Abd Elrahman TM. Clinical significance of plasma MMP-2 and MMP-9 levels as biomarkers for tumor expression in breast cancer patients in Egypt. Mol Biol Rep. 2020;47(2):1153\u201360.","journal-title":"Mol Biol Rep"},{"issue":"7","key":"613_CR50","doi-asserted-by":"publisher","first-page":"3619","DOI":"10.21873\/anticanres.14351","volume":"40","author":"SG Dofara","year":"2020","unstructured":"Dofara SG, Chang SL, Diorio C. Gene polymorphisms and circulating levels of MMP-2 and MMP-9: a review of their role in breast cancer risk. Anticancer Res. 2020;40(7):3619\u201331.","journal-title":"Anticancer Res"},{"key":"613_CR51","doi-asserted-by":"publisher","DOI":"10.3390\/ijms221910280","author":"JD Middleton","year":"2021","unstructured":"Middleton JD, Sivakumar S, Hai T. Chemotherapy-induced changes in the lung microenvironment the role of MMP-2 in facilitating intravascular arrest of breast cancer cells. Int J Mol Sci. 2021. https:\/\/doi.org\/10.3390\/ijms221910280.","journal-title":"Int J Mol Sci"},{"issue":"1","key":"613_CR52","first-page":"17","volume":"27","author":"MW Roomi","year":"2012","unstructured":"Roomi MW, Kalinovsky T, Roomi NW, Rath M, Niedzwiecki A. Anticancer effects of a specific mixture of nutrients in the multidrug-resistant human uterine sarcoma MES-SA\/Dx5 and the drug-sensitive MES-SA cell lines. Oncol Rep. 2012;27(1):17\u201327.","journal-title":"Oncol Rep"},{"issue":"15","key":"613_CR53","first-page":"3272","volume":"55","author":"M Yu","year":"1995","unstructured":"Yu M, Sato H, Seiki M, Thompson EW. Complex regulation of membrane-type matrix metalloproteinase expression and matrix metalloproteinase-2 activation by concanavalin A in MDA-MB-231 human breast cancer cells. Can Res. 1995;55(15):3272\u20137.","journal-title":"Can Res"},{"issue":"4","key":"613_CR54","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1111\/j.1349-7006.2010.01498.x","volume":"101","author":"H Sato","year":"2010","unstructured":"Sato H, Takino T. Coordinate action of membrane-type matrix metalloproteinase-1 (MT1-MMP) and MMP-2 enhances pericellular proteolysis and invasion. Cancer Sci. 2010;101(4):843\u20137.","journal-title":"Cancer Sci"},{"key":"613_CR55","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/1471-2407-9-20","volume":"9","author":"RC Figueira","year":"2009","unstructured":"Figueira RC, Gomes LR, Neto JS, Silva FC, Silva ID, Sogayar MC. Correlation between MMPs and their inhibitors in breast cancer tumor tissue specimens and in cell lines with different metastatic potential. BMC Cancer. 2009;9:20.","journal-title":"BMC Cancer"},{"issue":"53","key":"613_CR56","doi-asserted-by":"publisher","first-page":"41270","DOI":"10.1074\/jbc.M110.171595","volume":"285","author":"BH Koo","year":"2010","unstructured":"Koo BH, Han JH, Yeom YI, Kim DS. Thrombin-dependent MMP-2 activity is regulated by heparan sulfate. J Biol Chem. 2010;285(53):41270\u20139.","journal-title":"J Biol Chem"},{"issue":"6","key":"613_CR57","first-page":"1283","volume":"22","author":"MW Roomi","year":"2009","unstructured":"Roomi MW, Monterrey JC, Kalinovsky T, Niedzwiecki A, Rath M. Modulation of MMP-2 and MMP-9 by cytokines, mitogens and inhibitors in lung cancer and malignant mesothelioma cell lines. Oncol Rep. 2009;22(6):1283\u201391.","journal-title":"Oncol Rep"},{"issue":"3","key":"613_CR58","first-page":"605","volume":"23","author":"MW Roomi","year":"2010","unstructured":"Roomi MW, Monterrey JC, Kalinovsky T, Rath M, Niedzwiecki A. In vitro modulation of MMP-2 and MMP-9 in human cervical and ovarian cancer cell lines by cytokines, inducers and inhibitors. Oncol Rep. 2010;23(3):605\u201314.","journal-title":"Oncol Rep"},{"issue":"3","key":"613_CR59","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1007\/s10549-006-9335-4","volume":"102","author":"UW Nilsson","year":"2007","unstructured":"Nilsson UW, Garvin S, Dabrosin C. MMP-2 and MMP-9 activity is regulated by estradiol and tamoxifen in cultured human breast cancer cells. Breast Cancer Res Treat. 2007;102(3):253\u201361.","journal-title":"Breast Cancer Res Treat"},{"issue":"5","key":"613_CR60","doi-asserted-by":"publisher","first-page":"683","DOI":"10.4161\/cc.8.5.7703","volume":"8","author":"HA Kenny","year":"2009","unstructured":"Kenny HA, Lengyel E. MMP-2 functions as an early response protein in ovarian cancer metastasis. Cell Cycle. 2009;8(5):683\u20138.","journal-title":"Cell Cycle"},{"issue":"1","key":"613_CR61","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1186\/s13046-020-01685-w","volume":"39","author":"J Cui","year":"2020","unstructured":"Cui J, Dean D, Hornicek FJ, Chen Z, Duan Z. The role of extracelluar matrix in osteosarcoma progression and metastasis. J Exp Clin Cancer Res. 2020;39(1):178.","journal-title":"J Exp Clin Cancer Res"},{"key":"613_CR62","doi-asserted-by":"publisher","first-page":"259142","DOI":"10.1155\/2012\/259142","volume":"2012","author":"R Vishnubhotla","year":"2012","unstructured":"Vishnubhotla R, Bharadwaj S, Sun S, Metlushko V, Glover SC. Treatment with Y-27632, a ROCK inhibitor, increases the proinvasive nature of SW620 cells on 3D collagen type 1 matrix. Int J Cell Biol. 2012;2012:259142.","journal-title":"Int J Cell Biol"},{"key":"613_CR63","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.244848","author":"OY Revach","year":"2020","unstructured":"Revach OY, Grosheva I, Geiger B. Biomechanical regulation of focal adhesion and invadopodia formation. J Cell Sci. 2020. https:\/\/doi.org\/10.1242\/jcs.244848.","journal-title":"J Cell Sci"},{"issue":"6","key":"613_CR64","doi-asserted-by":"publisher","first-page":"3034","DOI":"10.1158\/0008-5472.CAN-05-2177","volume":"66","author":"VV Artym","year":"2006","unstructured":"Artym VV, Zhang Y, Seillier-Moiseiwitsch F, Yamada KM, Mueller SC. Dynamic interactions of cortactin and membrane type 1 matrix metalloproteinase at invadopodia: defining the stages of invadopodia formation and function. Can Res. 2006;66(6):3034\u201343.","journal-title":"Can Res"},{"issue":"11","key":"613_CR65","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.1038\/labinvest.3700674","volume":"87","author":"R Vishnubhotla","year":"2007","unstructured":"Vishnubhotla R, Sun S, Huq J, Bulic M, Ramesh A, Guzman G, et al. ROCK-II mediates colon cancer invasion via regulation of MMP-2 and MMP-13 at the site of invadopodia as revealed by multiphoton imaging. Lab Invest. 2007;87(11):1149\u201358.","journal-title":"Lab Invest"},{"issue":"1","key":"613_CR66","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1186\/s12885-022-09424-4","volume":"22","author":"V Manuelli","year":"2022","unstructured":"Manuelli V, Cahill F, Wylie H, Gillett C, Correa I, Heck S, et al. Invadopodia play a role in prostate cancer progression. BMC Cancer. 2022;22(1):386.","journal-title":"BMC Cancer"},{"issue":"2","key":"613_CR67","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1002\/pros.22735","volume":"74","author":"KL Burger","year":"2014","unstructured":"Burger KL, Learman BS, Boucherle AK, Sirintrapun SJ, Isom S, Diaz B, et al. Src-dependent Tks5 phosphorylation regulates invadopodia-associated invasion in prostate cancer cells. Prostate. 2014;74(2):134\u201348.","journal-title":"Prostate"},{"key":"613_CR68","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.semcancer.2019.08.003","volume":"62","author":"K Karamanou","year":"2020","unstructured":"Karamanou K, Franchi M, Vynios D, Brezillon S. Epithelial-to-mesenchymal transition and invadopodia markers in breast cancer: Lumican a key regulator. Semin Cancer Biol. 2020;62:125\u201333.","journal-title":"Semin Cancer Biol"},{"issue":"10","key":"613_CR69","doi-asserted-by":"publisher","first-page":"1657","DOI":"10.1007\/s00432-013-1484-3","volume":"139","author":"JA Choi","year":"2013","unstructured":"Choi JA, Lim IK. TIS21\/BTG2 inhibits invadopodia formation by downregulating reactive oxygen species level in MDA-MB-231 cells. J Cancer Res Clin Oncol. 2013;139(10):1657\u201365.","journal-title":"J Cancer Res Clin Oncol"},{"key":"613_CR70","doi-asserted-by":"publisher","first-page":"638311","DOI":"10.3389\/fonc.2021.638311","volume":"11","author":"SS Huang","year":"2021","unstructured":"Huang SS, Liao WY, Hsu CC, Chan TS, Liao TY, Yang PM, et al. A novel invadopodia-specific marker for invasive and pro-metastatic cancer stem cells. Front Oncol. 2021;11:638311.","journal-title":"Front Oncol"},{"issue":"4","key":"613_CR71","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1016\/j.bbrc.2019.12.009","volume":"522","author":"X Yan","year":"2020","unstructured":"Yan X, Cao N, Chen Y, Lan HY, Cha JH, Yang WH, et al. MT4-MMP promotes invadopodia formation and cell motility in FaDu head and neck cancer cells. Biochem Biophys Res Commun. 2020;522(4):1009\u201314.","journal-title":"Biochem Biophys Res Commun"},{"issue":"1","key":"613_CR72","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.1186\/s12885-019-6429-z","volume":"19","author":"C Benzing","year":"2019","unstructured":"Benzing C, Lam H, Tsang CM, Rimmer A, Arroyo-Berdugo Y, Calle Y, et al. TIMP-2 secreted by monocyte-like cells is a potent suppressor of invadopodia formation in pancreatic cancer cells. BMC Cancer. 2019;19(1):1214.","journal-title":"BMC Cancer"},{"issue":"11","key":"613_CR73","doi-asserted-by":"publisher","first-page":"166521","DOI":"10.1016\/j.bbadis.2022.166521","volume":"1868","author":"J Wu","year":"2022","unstructured":"Wu J, Liu X, Wu J, Lou C, Zhang Q, Chen H, et al. CXCL12 derived from CD248-expressing cancer-associated fibroblasts mediates M2-polarized macrophages to promote nonsmall cell lung cancer progression. Biochim Biophys Acta Mol Basis Dis. 2022;1868(11):166521.","journal-title":"Biochim Biophys Acta Mol Basis Dis"}],"container-title":["Discover Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12672-023-00613-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12672-023-00613-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12672-023-00613-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,13]],"date-time":"2023-01-13T19:19:29Z","timestamp":1673637569000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12672-023-00613-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,13]]},"references-count":73,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["613"],"URL":"https:\/\/doi.org\/10.1007\/s12672-023-00613-6","relation":{},"ISSN":["2730-6011"],"issn-type":[{"value":"2730-6011","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,13]]},"assertion":[{"value":"1 January 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 January 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 January 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study protocol was approved by the Ethics Committee of Tongji Hospital, Tongji University School of Medicine. Clinical specimens were obtained with patients\u2019 written informed consents and all experiments regarding patients\u2019 tissue samples were conducted in accordance with the Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent for participation"}},{"value":"The authors declare no competing interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"5"}}