Mutual Activation Between Cancer-Associated Fibroblasts And Cancer Cells Facilitates Growth And Progression Of Gastric Cancer

Objective: The study aimed to investigate the mutual interaction between cancer-associated fibroblasts (CAFs) and gastric cancer cells. Methods: Cell proliferation was determined using MTT assay. The characteristic proteins of CAFs were examined by immunohistochemistry assay, western blot, and real time-quantitative polymerase chain reaction. The effect of CAFs in promotion of tumor growth and progression was evaluated in gastric tumor-bearing mice. Results: We confirmed that CAFs promote proliferation and migration of gastric cancer cells (MKN-45). Co-incubation of normal human fibroblast cells (BJ cells) with MKN-45-conditioned medium resulted in overexpression of biomarkers of CAFs, such as FAP, alpha-SMA, MMP, GAL-1, PDGFR beta, and VIM. Furthermore, the mice co-implanted with MKN-45 cells and CAFs exhibited the rapidest tumor growth rate and shortest survival time when compared with others. Tumors of mice injected with MKN-45 cells and BJ cells progressed faster than those of mice injected only with MKN-45 cells. Further immunohistochemical assay revealed that tumor tissues of the MKN-45 + CAF group displayed the most obvious vasculature formation, which facilitates tumor progression and metastasis. Conclusion: Normal fibroblasts in a tumor microenvironment can be induced into CAFs and in turn promote tumor growth and progression.