Colorectal cancer cells induce the formation of cancer-associated fibroblasts by activating the ERK signaling pathway in fibroblasts.
10.12122/j.issn.1673-4254.2023.06.09
- Author:
Ting DENG
1
;
Boyu DU
1
;
Xueyan XI
1
Author Information
1. Department of Immunology, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan 442000, China.
- Publication Type:Journal Article
- Keywords:
ERK singaling;
cancer-associated fibroblasts;
colorectal cancer;
tumor microenvironment
- MeSH:
Humans;
Cancer-Associated Fibroblasts/metabolism*;
Culture Media, Conditioned/pharmacology*;
MAP Kinase Signaling System;
Caco-2 Cells;
Fibroblasts;
Signal Transduction;
Cell Proliferation;
Cell Line, Tumor;
Colorectal Neoplasms/genetics*;
Cell Movement
- From:
Journal of Southern Medical University
2023;43(6):943-951
- CountryChina
- Language:Chinese
-
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 upregulated 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.
