Mutual activation between cancer-associated fibroblasts and cancer cells facilitates growth and progression of gastric cancer

Hao Lin; Xiyou Cao; Yan Wang; Man Wang; Lin Liang; Zhenliang Sun; Jifa Zhang

Mutual activation between cancer-associated fibroblasts and cancer cells facilitates growth and progression of gastric cancer

Int J Clin Exp Pathol. 2020 Oct 1;13(10):2691-2700. eCollection 2020.

Authors

Hao Lin¹, Xiyou Cao², Yan Wang², Man Wang³, Lin Liang³, Zhenliang Sun³, Jifa Zhang³

Affiliations

¹ Medical College, Anhui University of Science and Technology Huainan, Anhui, China.
² Shanghai Putuo District Liqun Hospital Shanghai, China.
³ Fengxian Hospital Affiliated to Anhui University of Science and Technology Shanghai, China.

PMID: 33165335
PMCID: PMC7642703

Abstract

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, α-SMA, MMP, GAL-1, PDGFRβ, 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.

Keywords: Tumor microenvironment (TME); cancer-associated fibroblasts (CAFs); fibroblast activation protein (FAP); gastric cancer; α-smooth muscle actin (α-SMA).