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Interleukin-6 in cervical cancer: the relationship with vascular endothelial growth factor.
Wei, L H; Kuo, M L; Chen, C A; Cheng, W F; Cheng, S P; Hsieh, F J; Hsieh, C Y.
Afiliação
  • Wei LH; Department of Obstetrics and Gynecology, Institute of Toxicology, Tapei, Taiwan.
Gynecol Oncol ; 82(1): 49-56, 2001 Jul.
Article em En | MEDLINE | ID: mdl-11426961
OBJECTIVE: Interleukin-6 (IL-6), a central proinflammatory cytokine, has been implicated in cervical cancer, though its role remains elusive. This study was an attempt to elucidate the role of IL-6 in the pathogenesis of cervical cancer, with particular emphasis on tumor angiogenesis. METHODS: Cytosolic IL-6, vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) levels were determined via enzyme immunoassay in 60 FIGO stage IB-IIA cervical cancer patients. Immunohistochemical staining in tissue sections was performed to analyze the distributions of IL-6 and IL-6 receptors. Meanwhile, human papillomavirus (HPV) DNA was detected by polymerase chain reaction-based survey. In vitro studies of two cervical cancer cell lines, C33A and SiHa, for the interaction between IL-6 and VEGF were also performed. RESULTS: Consistently higher expression of IL-6 and VEGF was evident in cancerous tissues than in adjacent noncancer tissues in early-stage cervical cancer patients (P < 0.01). After recombinant human IL-6 was added, VEGF was induced in a time- and dose-dependent manner in cervical cancer cell line C33A. Correspondingly, interrupting the IL-6 autocrine machinery with either anti-IL-6 or anti-IL-6 receptor antibody markedly reduced the expression of VEGF at the transcriptional level in SiHa cells. Significantly higher levels of IL-6 in cancer tissues were observed in patients older than 45 (P < 0.01), patients with tumors >2 cm (P < 0.01), patients with oncogenic HPV-16 or -18 infections (P < 0.01), and patients with squamous cell carcinoma (P = 0.02). Patients with a deeper stromal invasion, vaginal invasion, lymphovascular emboli, or lymph node metastasis appeared to have higher intratumoral IL-6 levels, although the differences were statistically insignificant. CONCLUSIONS: Substantially high microenvironmental IL-6 levels promote tumor angiogenesis and the development of cervical cancer. Thus, inhibition of the biological activity of IL-6 may be potentially beneficial.
Assuntos
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Base de dados: MEDLINE Assunto principal: Endotélio Vascular / Carcinoma de Células Escamosas / Neoplasias do Colo do Útero / Fatores de Crescimento Endotelial / Linfocinas / Interleucina-6 Idioma: En Ano de publicação: 2001 Tipo de documento: Article
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Base de dados: MEDLINE Assunto principal: Endotélio Vascular / Carcinoma de Células Escamosas / Neoplasias do Colo do Útero / Fatores de Crescimento Endotelial / Linfocinas / Interleucina-6 Idioma: En Ano de publicação: 2001 Tipo de documento: Article