Carcinoma-Associated Fibroblasts Affect Oral Cancer Via Epithelial-Like Transformation

Carcinoma-associated fibroblasts (CAFs) are one of the most important stromal cells in the tumor microenvironment and promote cancer progression through “crosstalk” with cancer cells. We discovered a new phenomenon that oral CAFs showed epithelial-like shape. Therefore, we further investigated whether oral CAFs can transform into epithelial-like cells, and whether CAFs that underwent epithelial-like transition (ET-CAFs) affect the biological characteristics of oral squamous cell carcinoma (OSCC). Primary CAFs were isolated and purified from human OSCC tissue, and were identified via immunocytochemistry. Then, CAFs were transfected with lentivirus of Oct-4, Klf4, Sox2, and c-Myc (OKSM). Western blot was performed to identify ET-CAFs. Cell counting kit-8 assay, transwell invasion, and scratch wound healing assays were used to explore proliferation, invasion, and migration of ET-CAFs; With same assays, ET-CAFs were co-cultured with Cal27 to study whether they affect biological characteristics of Cal27, namely OSCC cells. Purified oral CAFs showed negative expression of E-Cadherin and Pan-CK. Epithelial-like cells were observed after OKSM transfection of CAFs and transfection in the order of OK-M-S can obtain more ET-CAFs. ET-CAFs showed positive expression of Pan-CK and significantly enhanced proliferation, but no significant changes in their invasion and migration. Moreover, ET-CAFs enhanced the proliferation, invasion, and migration of Cal27, with statistically significant differences. Oral CAFs can undergo epithelial-like transition. ET-CAFs exhibited enhanced proliferation and promoted the proliferation, invasion, and migration of OSCC.