Regulation of ovarian carcinoma SKOV-3 cell proliferation and secretion of MMPs by autocrine IL-6.
BACKGROUND
Cancerous ovarian tissues contain and produce high levels of pro-inflammatory cytokines (IL-1, IL-6 and TNF-alpha). 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.


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.


CONCLUSIONS
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.
Rabinovich
Alex
A
Unit of Gynecologic Oncology, Division of Obstetrics and Gynecology, Soroka University Medical Center, Beer-Sheva, Israel.
Medina
Liat
L
Piura
Benjamin
B
Segal
Shraga
S
Huleihel
Mahmoud
M
D000906:Antibodies / Q000494:pharmacology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology*
D000906:Antibodies; D015850:Interleukin-6; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9