{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T16:02:37Z","timestamp":1793289757788,"version":"4.5.0"},"reference-count":39,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2019LZL005"],"award-info":[{"award-number":["ZR2019LZL005"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["International Immunopharmacology"],"published-print":{"date-parts":[[2025,6]]},"DOI":"10.1016\/j.intimp.2025.114947","type":"journal-article","created":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T10:40:01Z","timestamp":1748256001000},"page":"114947","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":19,"special_numbering":"C","title":["TAMs-derived SPP1, regulated by HIF-1\u03b1\/STAT3 signaling pathway, influences colorectal cancer malignant progression by activation of EMT via integrin \u03b1v\u03b23"],"prefix":"10.1016","volume":"159","author":[{"given":"Yaru","family":"Qu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingchen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junnan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyuan","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuzhen","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.intimp.2025.114947_bb0005","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"10.1016\/j.intimp.2025.114947_bb0010","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1016\/S0140-6736(13)61649-9","article-title":"Colorectal cancer","volume":"383","author":"Brenner","year":"2014","journal-title":"Lancet"},{"key":"10.1016\/j.intimp.2025.114947_bb0015","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1038\/nm.3175","article-title":"A colorectal cancer classification system that associates cellular phenotype and responses to therapy","volume":"19","author":"Sadanandam","year":"2013","journal-title":"Nat. Med."},{"key":"10.1016\/j.intimp.2025.114947_bb0020","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1038\/nm.3174","article-title":"Vermeulen, Poor-prognosis colon cancer is defined by a molecularly distinct subtype and develops from serrated precursor lesions","volume":"19","author":"De Sousa","year":"2013","journal-title":"Nat. Med."},{"key":"10.1016\/j.intimp.2025.114947_bb0025","doi-asserted-by":"crossref","first-page":"5904","DOI":"10.1038\/onc.2008.271","article-title":"The tumor microenvironment and its role in promoting tumor growth","volume":"27","author":"Whiteside","year":"2008","journal-title":"Oncogene"},{"key":"10.1016\/j.intimp.2025.114947_bb0030","doi-asserted-by":"crossref","DOI":"10.1016\/j.pharmthera.2020.107753","article-title":"Tumor microenvironment as a therapeutic target in cancer","volume":"221","author":"Xiao","year":"2021","journal-title":"Pharmacol. Ther."},{"key":"10.1016\/j.intimp.2025.114947_bb0035","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.cell.2010.01.025","article-title":"Immunity, inflammation, and cancer","volume":"140","author":"Grivennikov","year":"2010","journal-title":"Cell"},{"key":"10.1016\/j.intimp.2025.114947_bb0040","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1016\/j.ccell.2022.02.013","article-title":"Immune phenotypic linkage between colorectal cancer and liver metastasis","volume":"40","author":"Liu","year":"2022","journal-title":"Cancer Cell"},{"key":"10.1016\/j.intimp.2025.114947_bb0045","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.yexcr.2017.08.028","article-title":"Upregulation of PD-L1 by SPP1 mediates macrophage polarization and facilitates immune escape in lung adenocarcinoma","volume":"359","author":"Zhang","year":"2017","journal-title":"Exp. Cell Res."},{"key":"10.1016\/j.intimp.2025.114947_bb0050","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/s40246-023-00558-5","article-title":"SPP1 is associated with adverse prognosis and predicts immunotherapy efficacy in penile cancer","volume":"17","author":"Zou","year":"2023","journal-title":"Hum Genomics."},{"key":"10.1016\/j.intimp.2025.114947_bb0055","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1186\/s12885-022-10485-8","article-title":"SPP1 is a prognostic related biomarker and correlated with tumor-infiltrating immune cells in ovarian cancer","volume":"22","author":"Gao","year":"2022","journal-title":"BMC Cancer"},{"key":"10.1016\/j.intimp.2025.114947_bb0060","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/bs.acc.2023.11.002","article-title":"Osteopontin in cancer","volume":"118","author":"Kumari","year":"2024","journal-title":"Adv. Clin. Chem."},{"key":"10.1016\/j.intimp.2025.114947_bb0065","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2021.749210","article-title":"Characterizing Intercellular Communication of Pan-Cancer Reveals SPP1+ Tumor-Associated Macrophage Expanded in Hypoxia and Promoting Cancer Malignancy Through Single-Cell RNA-Seq Data","volume":"9","author":"Wei","year":"2021","journal-title":"Front Cell Dev Biol."},{"key":"10.1016\/j.intimp.2025.114947_bb0070","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1080\/08830185.2021.1955876","article-title":"Lactic acid in macrophage polarization: The significant role in inflammation and cancer","volume":"41","author":"Zhou","year":"2022","journal-title":"Int. Rev. Immunol."},{"key":"10.1016\/j.intimp.2025.114947_bb0075","article-title":"Lactate: A regulator of immune microenvironment and a clinical prognosis indicator in colorectal cancer","volume":"13","author":"Zhu","year":"2022","journal-title":"Front. Immunol."},{"key":"10.1016\/j.intimp.2025.114947_bb0080","doi-asserted-by":"crossref","first-page":"3256","DOI":"10.4161\/cc.9.16.12553","article-title":"Oxidative stress in cancer associated fibroblasts drives tumor-stroma co-evolution: A new paradigm for understanding tumor metabolism, the field effect and genomic instability in cancer cells","volume":"9","author":"Martinez-Outschoorn","year":"2010","journal-title":"Cell Cycle"},{"key":"10.1016\/j.intimp.2025.114947_bb0085","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s13577-021-00622-z","article-title":"Lactate shuttle: from substance exchange to regulatory mechanism","volume":"35","author":"Wang","year":"2022","journal-title":"Hum. Cell"},{"key":"10.1016\/j.intimp.2025.114947_bb0090","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.cell.2015.03.011","article-title":"A lactate-induced response to hypoxia","volume":"161","author":"Lee","year":"2015","journal-title":"Cell"},{"key":"10.1016\/j.intimp.2025.114947_bb0095","doi-asserted-by":"crossref","first-page":"2550","DOI":"10.1158\/0008-5472.CAN-10-2828","article-title":"Lactate influx through the endothelial cell monocarboxylate transporter MCT1 supports an NF-\u03baB\/IL-8 pathway that drives tumor angiogenesis","volume":"71","author":"V\u00e9gran","year":"2011","journal-title":"Cancer Res."},{"key":"10.1016\/j.intimp.2025.114947_bb0100","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2024.113470","article-title":"Colorectal cancer cells establish metabolic reprogramming with cancer-associated fibroblasts (CAFs) through lactate shuttle to enhance invasion, migration, and angiogenesis","volume":"143","author":"Wang","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.intimp.2025.114947_bb0105","series-title":"GEPIA (Gene Expression Profiling Interactive Analysis). http:\/\/www.gepia. cancer-puk\/","year":"2023"},{"key":"10.1016\/j.intimp.2025.114947_bb0110","unstructured":"TIGER (Tumor Immunotherapy Gene Expression Resource). http:\/\/ http:\/\/tiger.canceromics.org\/, 2023 (accessed 15 April 2023)."},{"key":"10.1016\/j.intimp.2025.114947_bb0115","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.cmet.2019.06.001","article-title":"Macrophages and Metabolism in the Tumor Microenvironment","volume":"30","author":"Vitale","year":"2019","journal-title":"Cell Metab."},{"key":"10.1016\/j.intimp.2025.114947_bb0120","doi-asserted-by":"crossref","unstructured":"F. Bray, J. Ferlay, I. Soerjomataram, R.L. Siegel, L.A. Torre, et al, Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries, CA Cancer J. Clin. 68 (2018) 394\u2013424, doi:https:\/\/doi.org\/10.3322\/caac.21492.","DOI":"10.3322\/caac.21492"},{"key":"10.1016\/j.intimp.2025.114947_bb0125","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.3390\/ijms22041565","article-title":"The Role of Tumor Microenvironment Cells in Colorectal Cancer (CRC) Cachexia","volume":"22","author":"Kasprzak","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.intimp.2025.114947_bb0130","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1158\/1078-0432.CCR-22-2041","article-title":"Colorectal Cancer Metastases in the Liver Establish Immunosuppressive Spatial Networking between Tumor-Associated SPP1+ Macrophages and Fibroblasts","volume":"29","author":"Sathe","year":"2023","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.intimp.2025.114947_bb0135","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1038\/s41467-022-29366-6","article-title":"Single-cell and spatial analysis reveal interaction of FAP+ fibroblasts and SPP1+ macrophages in colorectal cancer","volume":"13","author":"Qi","year":"2022","journal-title":"Nat. Commun."},{"key":"10.1016\/j.intimp.2025.114947_bb0140","doi-asserted-by":"crossref","first-page":"1185208","DOI":"10.3389\/fimmu.2023.1185208","article-title":"ANGPTL2+cancer-associated fibroblasts and SPP1+macrophages are metastasis accelerators of colorectal cancer","volume":"14","author":"Liu","year":"2023","journal-title":"Front. Immunol."},{"key":"10.1016\/j.intimp.2025.114947_bb0145","article-title":"AQP9 transports lactate in tumor-associated macrophages to stimulate an M2-like polarization that promotes colon cancer progression","volume":"31","author":"Shi","year":"2022","journal-title":"Biochem Biophys Rep."},{"key":"10.1016\/j.intimp.2025.114947_bb0150","doi-asserted-by":"crossref","first-page":"456","DOI":"10.3389\/fonc.2019.00456","article-title":"IL-4\/IL-13 Stimulated Macrophages Enhance Breast Cancer Invasion Via Rho-GTPase Regulation of Synergistic VEGF\/CCL-18 Signaling","volume":"9","author":"Little","year":"2019","journal-title":"Front. Oncol."},{"key":"10.1016\/j.intimp.2025.114947_bb0155","doi-asserted-by":"crossref","first-page":"3591","DOI":"10.1038\/s41388-023-02869-2","article-title":"Alleviating hypoxia to improve cancer immunotherapy","volume":"42","author":"Fan","year":"2023","journal-title":"Oncogene"},{"key":"10.1016\/j.intimp.2025.114947_bb0160","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1038\/s41586-023-06409-6","article-title":"Lactate limits CNS autoimmunity by stabilizing HIF-1\u03b1 in dendritic cells","volume":"620","author":"Sanmarco","year":"2023","journal-title":"Nature"},{"key":"10.1016\/j.intimp.2025.114947_bb0165","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2023.112945","article-title":"HIF-1\u03b1 drives resistance to ferroptosis in solid tumors by promoting lactate production and activating SLC1A1","volume":"42","author":"Yang","year":"2023","journal-title":"Cell Rep."},{"key":"10.1016\/j.intimp.2025.114947_bb0170","doi-asserted-by":"crossref","first-page":"3363","DOI":"10.1038\/s41467-021-23448-7","article-title":"A small molecule HIF-1\u03b1 stabilizer that accelerates diabetic wound healing","volume":"12","author":"Li","year":"2021","journal-title":"Nat. Commun."},{"key":"10.1016\/j.intimp.2025.114947_bb0175","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.molmet.2019.07.006","article-title":"Monocarboxylate transporters in cancer","volume":"33","author":"Payen","year":"2020","journal-title":"Mol Metab."},{"key":"10.1016\/j.intimp.2025.114947_bb0180","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.diff.2022.10.001","article-title":"Macrophage polarization in THP-1 cell line and primary monocytes: a systematic review","volume":"128","author":"Mohd Yasin","year":"2022","journal-title":"Differentiation"},{"key":"10.1016\/j.intimp.2025.114947_bb0185","doi-asserted-by":"crossref","DOI":"10.1016\/j.metabol.2024.156027","article-title":"Beyond glucose: The crucial role of redox signaling in \u03b2-cell metabolic adaptation","volume":"161","author":"Holendov\u00e1","year":"2024","journal-title":"Metabolism"},{"key":"10.1016\/j.intimp.2025.114947_bb0190","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.cytogfr.2022.07.004","article-title":"Correlation between PD-1\/PD-L1 expression and polarization in tumor-associated macrophages: A key player in tumor immunotherapy","volume":"67","author":"Li","year":"2022","journal-title":"Cytokine Growth Factor Rev."},{"key":"10.1016\/j.intimp.2025.114947_bb0195","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2022.111929","article-title":"Spatial and single-cell transcriptomics decipher the cellular environment containing HLA-G+ cancer cells and SPP1+ macrophages in colorectal cancer","volume":"42","author":"Ozato","year":"2023","journal-title":"Cell Rep."}],"container-title":["International Immunopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1567576925009373?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1567576925009373?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T17:57:05Z","timestamp":1778522225000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1567576925009373"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":39,"alternative-id":["S1567576925009373"],"URL":"https:\/\/doi.org\/10.1016\/j.intimp.2025.114947","relation":{},"ISSN":["1567-5769"],"issn-type":[{"value":"1567-5769","type":"print"}],"subject":[],"published":{"date-parts":[[2025,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"TAMs-derived SPP1, regulated by HIF-1\u03b1\/STAT3 signaling pathway, influences colorectal cancer malignant progression by activation of EMT via integrin \u03b1v\u03b23","name":"articletitle","label":"Article Title"},{"value":"International Immunopharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.intimp.2025.114947","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"114947"}}