PMID- 36737590 OWN - NLM STAT- MEDLINE DCOM- 20230213 LR - 20230304 IS - 1559-131X (Electronic) IS - 1357-0560 (Linking) VI - 40 IP - 3 DP - 2023 Feb 3 TI - CAFs secrete CXCL12 to accelerate the progression and cisplatin resistance of colorectal cancer through promoting M2 polarization of macrophages. PG - 90 LID - 10.1007/s12032-023-01953-7 [doi] AB - The purpose of this study was to investigate the effect of the interaction between tumor-associated fibroblasts (CAFs) and macrophage polarization on colorectal cancer (CRC) progression. Clinical tissue samples of CRC and health volunteers were collected to isolate normal fibroblasts (NFs) and CAFs. LoVo, HCT116, or THP-1 cells were co-cultured with NFs or CAFs. Immunofluorescence and western blot detected the expression of related markers. MTT assay measured cell viability and IC50. Cell proliferation and metastasis were detected through colony formation and transwell assays. CRC mice models were constructed by injection of HCT116 cells, with IHC assessing C-X-C Motif Chemokine Ligand 12 (CXCL12) expression. The proliferation, migration, invasion, and cisplatin (DDP) resistance of CRC cells were apparently increased after co-culture with CAFs. Compared to NFs, CAFs have a markedly higher ability to recruit macrophages and promote macrophages M2 polarization by secreting CXCL12. Further experiments affirmed that CXCL12 secreted by CAFs boosted proliferation, migration, invasion, and DDP resistance of CRC cells via induction of the M2 polarization of macrophages. In vivo experiments confirmed that CAFs promoted the progression of CRC and DDP resistance by affecting M2 polarization through CXCL12. CAFs recruit macrophages and secrete CXCL12 to induce M2 polarization of macrophages, thus mediating cell function and DDP resistance of CRC. CI - (c) 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Jiang, Hang AU - Jiang H AD - Department of Gastroenterology, The Yancheng School of Clinical Medicine of Nanjing Medical University (Yancheng Third People's Hospital), Yancheng, 224008, Jiangsu, China. FAU - Ge, Haijue AU - Ge H AD - Department of Gastroenterology, The Yancheng School of Clinical Medicine of Nanjing Medical University (Yancheng Third People's Hospital), Yancheng, 224008, Jiangsu, China. FAU - Shi, Yuanyuan AU - Shi Y AD - Department of Central Laboratory, The Yancheng School of Clinical Medicine of Nanjing Medical University (Yancheng Third People's Hospital), Yancheng, 224008, Jiangsu, China. FAU - Yuan, Fang AU - Yuan F AD - Department of Central Laboratory, The Yancheng School of Clinical Medicine of Nanjing Medical University (Yancheng Third People's Hospital), Yancheng, 224008, Jiangsu, China. FAU - Yue, Hongqin AU - Yue H AUID- ORCID: 0000-0002-4159-4963 AD - Department of Gastroenterology, The Yancheng School of Clinical Medicine of Nanjing Medical University (Yancheng Third People's Hospital), Yancheng, 224008, Jiangsu, China. yuehqqy1999@126.com. LA - eng PT - Journal Article DEP - 20230203 PL - United States TA - Med Oncol JT - Medical oncology (Northwood, London, England) JID - 9435512 RN - Q20Q21Q62J (Cisplatin) RN - 0 (Chemokine CXCL12) SB - IM MH - Animals MH - Mice MH - Cell Line, Tumor MH - Cell Movement/physiology MH - Cell Proliferation MH - *Cisplatin/pharmacology MH - *Colorectal Neoplasms/pathology MH - Macrophages/metabolism MH - Tumor Microenvironment MH - Fibroblasts/metabolism MH - Chemokine CXCL12/metabolism OTO - NOTNLM OT - CXCL12 OT - Cancer-associated fibroblast OT - Colorectal cancer OT - Macrophages M2 polarization OT - Tumor microenvironment EDAT- 2023/02/04 06:00 MHDA- 2023/02/08 06:00 CRDT- 2023/02/03 23:39 PHST- 2022/08/23 00:00 [received] PHST- 2023/01/15 00:00 [accepted] PHST- 2023/02/03 23:39 [entrez] PHST- 2023/02/04 06:00 [pubmed] PHST- 2023/02/08 06:00 [medline] AID - 10.1007/s12032-023-01953-7 [pii] AID - 10.1007/s12032-023-01953-7 [doi] PST - epublish SO - Med Oncol. 2023 Feb 3;40(3):90. doi: 10.1007/s12032-023-01953-7.