Effects of cancer-associated fibroblasts deletion using HSVtk suicide system in OSCC.
Oral Diseases(2023)
摘要
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.
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关键词
fibroblasts deletion,cancer‐associated,suicide system
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