Regulation of ovarian carcinoma SKOV-3 cell proliferation and secretion of MMPs by autocrine IL-6

Alex Rabinovich, Liat Medina, Benjamin Piura, Shraga Segal, Mahmoud Huleihel

Research output: Contribution to journalArticlepeer-review

64 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)267-272
Number of pages6
JournalAnticancer Research
Volume27
Issue number1 A
StatePublished - 1 Jan 2007

Keywords

  • IL-6
  • MMP-2
  • MMP-9
  • Ovarian cancer
  • Zymography

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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