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 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.
Department of Otorhinolaryngology, Medical University of Innsbruck, Innsbruck, Austria.
Teresa Bernadette
TB
Steinbichler
Department of Otorhinolaryngology, Medical University of Innsbruck, Innsbruck, Austria.
Veronika
V
Metzler
Department of Otorhinolaryngology, Medical University of Innsbruck, Innsbruck, Austria.
Christian
C
Pritz
Department of Otorhinolaryngology, Medical University of Innsbruck, Innsbruck, Austria.
Herbert
H
Riechelmann
Department of Otorhinolaryngology, Medical University of Innsbruck, Innsbruck, Austria.
Jozsef
J
Dudas
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology*; D049109:Cell Proliferation; D002945:Cisplatin / Q000494:pharmacology*; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005881:Gingiva / Q000187:drug effects / Q000473:pathology*; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000473:pathology*; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D017077:Culture Media, Conditioned; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D002945:Cisplatin
TGF-β1; cancer-associated fibroblasts; chemoresistance; cisplatin; epithelial to mesenchymal transition