Overexpression of TGF-ß1 and SDF-1 in cervical cancer-associated fibroblasts promotes cell growth, invasion and migration.

OBJECTIVE: The purpose of this study was to investigate the effect of overexpression of transforming growth factor ß1 (TGF-ß1) and stromal cell-derived factor 1 (SDF-1) in cervical cancer-associated fibroblasts (CAFs) on regulating cell growth, invasion and migration. METHODS: CAF cells and normal fibroblast cells (NFs) were obtained from patients with cervical squamous cell carcinoma and multiple uterine leiomyomas, respectively. Immunofluorescence assay and western blot were used to determine the expression of Vimentin and α-smooth muscle actin (α-SMA). CCK-8 assay was used to detect cell viability. Giemsa dyer was used to detect the colony formation. Flow cytometry was used to detect the growth state of cells. Transwell assays were used to detect the migration and invasion. RESULTS: Vimentin and α-SMA expression in CAFs were significantly increased than those in NFs. In addition, TGF-ß1 and SDF-1 expression were notably increased, and transforming growth factor beta receptor 2 (TßRII) expression was markedly decreased in CAF cells than those in NFs. Similarly, TGF-ß1 and SDF-1 expression in the co-culture of CAFs and Hela cells were significantly increased, and cell proliferation, migration, invasion, colony formation and cell cycle progression were also promoted, while cell apoptosis was decreased. Those phenomena were reversed in the co-culture system with neutralizing antibodies to TGF-ß1 and SDF-1. Furthermore, exogenous TGF-ß1 and SDF-1 enhanced proliferation, colony formation, cell cycle progression, migration and invasion while decreased apoptosis of cells. These phenomena were also reversed by the addition of neutralizing antibodies to TGF-ß1 and SDF-1. CONCLUSION: Overexpression of TGF-ß1 and SDF-1 in CAFs can promote the growth, invasion and migration of cervical cancer cells.