Regulation of Ovarian Carcinoma SKOV-3 Cell Proliferation and Secretion of MMPs by Autocrine IL-6

• Published in: Anticancer research 2007-01, Vol.27 (1A), p.267-272
• Main Authors: RABINOVICH, Alex, MEDINA, Liat, PIURA, Benjamin, SEGAL, Shraga, HULEIHEL, Mahmoud
• Format: Article
• Language: English
• Subjects: Antibodies - pharmacology; Biological and medical sciences; Cell Growth Processes - physiology; Cell Line, Tumor; Dose-Response Relationship, Drug; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; Humans; Interleukin-6 - immunology; Interleukin-6 - pharmacology; Interleukin-6 - physiology; Interleukin-6 - secretion; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 2 - secretion; Matrix Metalloproteinase 9 - metabolism; Matrix Metalloproteinase 9 - secretion; Medical sciences; Ovarian Neoplasms - enzymology; Ovarian Neoplasms - pathology; Ovarian Neoplasms - secretion; Tumors
• ISSN: 0250-7005; 1791-7530

Background: Cancerous ovarian tissues contain and produce high levels of pro-inflammatory cytokines (IL-1, IL-6 and TNF-α). The aim of this study was to assess the mechanisms by which autocrine IL-6 affects the ovarian carcinoma continuous cell line (SKOV-3) tumorigenicity. Materials and Methods: Autocrine IL-6 was neutralized by the addition of anti-IL-6 antibodies to SKOV-3 cell cultures. The proliferation rate was evaluated by MMT staining and the capacity to produce matrix metalloproteinases (MMPs) 2 and 9 was examined by zymography. Results: The SKOV-3 cells secreted IL-6 in a time-dependent manner (24-96 h). The addition of anti-IL-6 antibodies to SKOV-3 cell cultures did not affect their proliferation rate within 96 h of incubation. In addition, SKOV-3 cells secreted MMP-2 and MMP-9 as confirmed by zymography. The MMP-9 levels decreased in a time-dependent manner (3, 8, 24 h) and the addition of anti-IL-6 antibodies to SKOV-3 cell cultures significantly decreased their capacity to secrete MMP-9, particularly after 8 h of incubation. MMP-2 (pro-active and active forms) was also secreted by SKOV-3 cell cultures but could be measured only after 24-96 h of incubation. The levels of MMP-2 increased in a time-dependent manner. The addition of anti-IL-6 antibodies to SKOV-3 cell cultures did not affect their capacity to secrete MMP-2. Conclusion: Our results suggest that IL-6 secreted by SKOV-3 cells could be involved in their tumorigenic potential, particularly potentiating their capacity to secrete MMP-9.