Role of IL-6 in neuroendocrine differentiation and chemosensitivity of non-small cell lung cancer.
Interleukin-6 (IL-6) has been shown to regulate both growth and neuroendocrine (NE) differentiation in some types of human cancer cells, and erbB2 may be a critical component of IL-6 signaling. Non-small cell lung cancer (NSCLC) tumors that demonstrate NE properties have been suggested to have biological characteristics similar to small cell lung cancers with initial responsiveness to chemotherapy. We investigated whether IL-6 is implicated in the cell growth, NE differentiation, and chemosensitivity of NSCLC-NE cells. NSCLC-NE cells were treated with exogenous IL-6, and a subclone of an IL-6-transfected NSCLC cell line that constitutively expressed IL-6 receptor was also generated. These cells were assessed for cell proliferation by cell counting and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assays, chemosensitivity to cisplatin and etoposide by MTT assays, and NE differentiation by observing morphological changes and immunoblotting for neuron-specific enolase (NSE). The IL-6-treated cells and the IL-6-transfected cells showed enhanced cell proliferation and downregulated NSE expression, but little change in chemosensitivity. In the culture medium, IL-6-transfected cells grew as looser aggregates than the parental cells. IL-6 could not activate the erbB genes. In conclusion, IL-6 can induce cell proliferation and NE dedifferentiation but has little effect on chemosensitivity in IL-6 receptor-expressing NSCLC-NE cells. The status of NSE expression is unlikely to be a crucial factor for chemosensitivity in NSCLC cells.
Chang
Kuo-Ting
KT
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
Huang
Chi-Ying F
CY
Tsai
Chun-Ming
CM
Chiu
Chao-Hua
CH
Lok
Ying-Yung
YY
D000970:Antineoplastic Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology*; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D004396:Coloring Agents; D015536:Down-Regulation; D066246:ErbB Receptors / Q000378:metabolism; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism* / Q000494:pharmacology; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D009490:Neurosecretory Systems / Q000473:pathology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D013778:Tetrazolium Salts; D013844:Thiazoles
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D004396:Coloring Agents; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles; D005047:Etoposide; D066246:ErbB Receptors; D010751:Phosphopyruvate Hydratase; C022616:thiazolyl blue; D002945:Cisplatin