Increased interleukin-6 expression is associated with poor prognosis and acquired cisplatin resistance in head and neck squamous cell carcinoma.
Increased expression of interleukin 6 (IL-6) is associated with poor prognosis and chemoresistance in many different carcinomas, but its role in head and neck squamous cell carcinoma (HNSCC) is still unsettled. Analyzing tumorous mRNA expression data from 399 HNSCC patients revealed that high IL-6 expression predicted poor prognosis. Similar tendency was observed in platinum treated patients, suggesting an IL-6 associated cisplatin resistance. IL-6 increase was also found in two in-house acquired cisplatin‑resistant HNSCC cell lines (both basaloid and conventional squamous cell carcinoma) by using microarray analysis. However, although the in-house acquired cisplatin-resistant cell lines had higher basal and markedly increased cisplatin-induced IL-6 expression, IL-6 did not mediate the cisplatin resistance as neither exogenous IL-6 nor IL-6R/gp130 inhibitors affected cisplatin sensitivity. Moreover, the IL-6/STAT3 pathway was impaired in the resistant cell lines, partly due to decreased IL-6R expression. Thus, high IL-6 expression correlated to poor prognosis and acquired cisplatin resistance, but it did not mediate cisplatin resistance in the HNSCC cell lines.
Department of Oral Biology, University of Oslo, Blindern, Oslo 0316, Norway.
Jian
J
Gao
Genome Biology Group, Department of Molecular Oncology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo 0424, Norway.
Sen
S
Zhao
Department of Oral Biology, University of Oslo, Blindern, Oslo 0316, Norway.
Trond S
TS
Halstensen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D015870:Gene Expression; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D055815:Young Adult
D000970:Antineoplastic Agents; C508600:IL6 protein, human; D015850:Interleukin-6; D002945:Cisplatin