Tumor-associated fibroblast-conditioned medium induces CDDP resistance in HNSCC cells

OBJECTIVE: EMT (epithelial to mesenchymal transition) contributes to tumor progression and metastasis. We aimed to investigate the effects of EMT on CDDP resistance in HNSCC (head and neck squamous cell carcinoma)-cells. METHODS: EMT was induced using conditioned medium from a tumor cell/fibroblast co-culture. HNSCC cells were alternatively treated with TGF-β1. The response to CDDP was evaluated with viability and clonogenic assays. RESULTS: Treatment of SCC-25/Detroit 562 cells with conditioned medium increased viability of the tumor cells. Moreover, it doubled the IC(50) of CDDP of SCC-25 cells from 6.2 μM to 13.1 μM (p < 0.001). The IC(50) of CDDP of Detroit 562 cells was increased following treatment with conditioned medium from 13.1 μM to 26.8 μM (p < 0.01). Colony forming ability after treatment with 5 or 10 μM CDDP was significantly higher in HNSCC cells treated with co-culture conditioned medium than in controls (p < 0.05). Treatment with TGF-β1 had no effect on the IC(50) of CDDP (p > 0.1). CONCLUSIONS: Cell free medium from a co-culture was able to induce EMT in HNSCC cells. Co-culture treated HNSCC cells revealed increased viability and were less sensitive to CDDP treatment. TGF-β1 also induced a mesenchymal phenotype, but did not alter resistance to CDDP in HNSCC cells.