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Objective To investigate the inflammatory induction effect of HCT-116 colorectal cancer cells on normal fibroblasts (NFs) extracted from para-cancerous tissues and the effect of cancer associated fibroblasts (CAFs) on cancer cell migration and its potential mechanism. Methods The enzyme digestive method was used to extract NFs and CAFs from tissues. Spatial Gene Expression Dataset was downloaded to analyze transcriptional expression levels of inflammatory factors including transforming growth factor β (TGF-β), tumor necrosis factor-α (TNF-α), C-X-C motif chemokine ligand 2 (CXCL2), interleukin-1β (IL-1β), and stromal cell-derived factor-1 (SDF-1). In vitro direct and indirect co-culture models were used to study the interaction between fibroblasts and cancer cells. Flow cytometry was used to detect expressions of fibroblast activated protein (FAP) and α-smooth muscle actin (α-SMA). Inflammatory factors TGF-β, TNF-α, CXCL2, IL-1β, and SDF-1 secreted in medium were measured by ELISA. Three co-culture groups were set up in which HCT-116 cells were co-cultured respectively with NFs, CAFs, and CAFs pretreated with AMD3100, an inhibitor of SDF-1. Cell migration ability was evaluated by the cell scratch-wound assay and the TranswellTM migration assay. Results CAFs expressed higher levels of FAP and α-SMA than NFs, and HCT-116 cancer cells induced the transformation of NFs to CAFs. Compared to NFs, CAFs secreted higher levels of inflammatory factors TGF-β, TNF-α, CXCL2, IL-1β, and SDF-1, while in the in vitro co-culture models cancer cells induced the secretion of SDF-1 but had no effect on secretions of TGF-β, TNF-α, CXCL2, and IL-1β from NFs. CAFs significantly stimulated cancer cell migration compared to NFs, which was weakened by AMD3100, an inhibitor of SDF-1. Conclusion Colorectal cancer cells induce the transformation of NFs to CAFs, and CAFs stimulated cancer cell migration with the SDF-1 secreted.


Lina Li, Yang Zhai, Yuzhen Wang, Liuqing Yang. Human colorectal cancer cells induce fibroblasts to secrete stromal cell-derived factor 1 (SDF-1) to stimulate cancer cell migration]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology. 2021 Sep;37(9):821-827

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PMID: 34533130

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