Tumor-associated fibroblast-conditioned medium induces CDDP resistance in HNSCC cells
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Teresa Bernadette Steinbichler1, Veronika Metzler1, Christian Pritz1, Herbert Riechelmann1 and Jozsef Dudas1
1 Department of Otorhinolaryngology, Medical University of Innsbruck, Innsbruck, Austria
Teresa Bernadette Steinbichler, email:
Keywords: epithelial to mesenchymal transition, chemoresistance, cisplatin, cancer-associated fibroblasts, TGF-β1
Received: May 20, 2015 Accepted: October 09, 2015 Published: October 21, 2015
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 IC50 of CDDP of SCC-25 cells from 6.2 μM to 13.1 μM (p < 0.001). The IC50 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 IC50 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.
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