Interleukin-6 directly influences proliferation and invasion potential of head and neck cancer cells.
Interleukin-6 (IL-6) is a multifunctional regulator of immune response and hematopoiesis. Recently, it has been reported that expression of IL-6 is correlated with prognosis in various cancer patients. In this study, we investigated whether the proliferation and invasion potential of head and neck squamous cell carcinomas (HNSCCs) were influenced by IL-6. All HNSCC cell lines, HEp-2, HSC-2, HSC-4, and SAS, were tested by reverse transcription-polymerase chain reaction (RT-PCR) and expressed the IL-6 receptor (IL-6R), and glycoprotein 130, which is responsible for signal transduction. HEp-2, HSC-2, and HSC-4 also produced IL-6. IL-6 inhibited the proliferation of HSC-2 and SAS, but the invasion potential of all the cell lines increased. Moreover, IL-6 down-regulated soluble IL-6R expression. Anti-IL-6R antibody abrogated the inhibited proliferation and increased invasion induced by IL-6. IL-6 stimulation also induced the extracellular regulated protein kinase 1/2 activation and increased vascular endothelial growth factor release. These results suggest that IL-6 can directly influence cell proliferation and the invasion potential as the first step of tumor metastasis.
Kanazawa
Takeharu
T
Department of Otolaryngology, Jichi Medical University, Omiya Medical Center, 857-1 Amanuma, Omiya Saitama City, Saitama, 330-8503, Japan. kanatake@omiya.jichi.ac.jp
Nishino
Hiroshi
H
Hasegawa
Masahiro
M
Ohta
Yasushi
Y
Iino
Yukiko
Y
Ichimura
Keiichi
K
Noda
Yutaka
Y
D000912:Antibodies, Neoplasm / Q000032:analysis; D014408:Biomarkers, Tumor / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics* / Q000276:immunology / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D012334:RNA, Neoplasm / Q000235:genetics*; D019947:Receptors, Interleukin-6 / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000912:Antibodies, Neoplasm; D014408:Biomarkers, Tumor; C508603:IL6R protein, human; D015850:Interleukin-6; D012334:RNA, Neoplasm; D019947:Receptors, Interleukin-6