Effects of cancer‐associated fibroblasts deletion using HSVtk suicide system in OSCC.

Objective: To evaluate the biological characteristics of oral cancer cells co‐cultured with cancer‐associated fibroblasts (CAFs)‐HSVtk and to assess the reliability of the CAFs‐HSVtk suicide system in a co‐culture model. Methods: CAFs were lentivirus‐transfected with PCDH‐HSVtk. Ganciclovir (GCV) was added and the survival rates of the CAFs‐HSVtk were measured. In parallel with the selective elimination of CAFs, comparison was made of the effects of CAF‐HSVtk on tumor cell proliferation/migration in a CAFs‐tumor co‐cultural system. Cell death of co‐cultured oral cancer cells was evaluated by flow cytometry. Results: Q‐PCR analysis showed that the expression of HSVtk in the CAFs‐HSVtk group was significantly higher than in the control group (p < 0.01). The survival rates of CAFs‐HSVtk with GCV were significantly reduced (p < 0.01). Following selective depletion of CAFs‐HSVtk, the growth and migration rates of oral cancer cells co‐cultured with CAFs‐HSVtk were reduced in a mixture ratio of 1:2 (p < 0.01, p < 0.01). Conclusions: Enhanced proliferation and migration rates of oral cancer cells in co‐culture were seriously impaired after deleting CAFs using the HSVtk suicide system, while oral tumor cell death was not affected. Therefore, CAFs‐HSVtk can be utilized as a valid model for CAF signature identification. [ABSTRACT FROM AUTHOR]