Journal of Southern Medical University ›› 2023, Vol. 43 ›› Issue (6): 943-951.doi: 10.12122/j.issn.1673-4254.2023.06.09
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DENG Ting, DU Boyu, XI Xueyan
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Abstract: Objective To investigate the mechanism by which conditioned medium of colorectal cancer cells promotes the formation of cancer-associated fibroblasts (CAFs). Methods Normal human colorectal fibroblasts (CCD-18Co cells) in logarithmic growth phase were treated with the conditioned media of colorectal cancer HCT116 cells (HCT116-CM) or Caco-2 cells (Caco-2-CM) alone or in combination with 300 nmol/L ERK inhibitor SCH772984. The expression levels of CAFs-related molecular markers were detected in the treated cells with real-time quantitative PCR (RT- qPCR) and immunofluorescence assay, and the changes in cell proliferation, colony formation and migration were assessed with RTCA, colony formation and wound healing assays; Western blotting was performed to detect the activated signaling pathways in the fibroblasts and the changes in CAFs formation after blocking of the signaling pathway. Results HCT116-CM and Caco-2-CM significantly up-regulated mRNA expression levels of CAFs markers (including α-SMA, FAP, FN and TGF-β) in CCD-18Co cells, and strongly promoted fibroblast transformation into CAFs (P<0.05). The two conditioned media also promoted the proliferation, colony formation and migration of CCD-18Co cells (P<0.05) and significantly increased the levels of α-SMA protein and ERK phosphorylation in the cells (P<0.05). The ERK inhibitor SCH772984 obviously inhibited the expression of α-SMA and the transformation of CCD-18Co cells into CAFs induced by the conditioned medium of colorectal cancer cells (P<0.05). Conclusion Colorectal cancer cells may induce the formation of colorectal CAFs by activating the ERK pathway in the fibroblasts.
Key words: tumor microenvironment; colorectal cancer; cancer-associated fibroblasts; ERK singaling
DENG Ting, DU Boyu, XI Xueyan. Colorectal cancer cells induce the formation of cancer-associated fibroblasts by activating the ERK signaling pathway in fibroblasts[J]. Journal of Southern Medical University, 2023, 43(6): 943-951.
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URL: https://www.j-smu.com/EN/10.12122/j.issn.1673-4254.2023.06.09
https://www.j-smu.com/EN/Y2023/V43/I6/943