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Multiple steps of HLA-G in ovarian carcinoma metastasis: alter NK cytotoxicity and induce matrix metalloproteinase-15 (MMP-15) expression.

Abstract
Previous study showed that aberrant HLA-G expression in cancer cells plays important roles in disease progression and it was associated with tumor metastasis and with poor survival in an animal model with ovarian cancer; however, the mechanisms remain to be explored. In this study, we found that HLA-G expression could dramatically decreased the NK cytotoxicity against the ovarian carcinoma cell line (HO-8910) engineered to express HLA-G (HO-8910-G), and matrix metalloproteinase-15 (MMP-15) expression was up-regulated in HO-8910-G cells. Consistent with this, a strong correlation between HLA-G and MMP-15 expression were observed in a cohort of ovarian cancer samples. Knockdown the HLA-G induced MMP-15 expression by small interfere RNA (siRNA) significantly decreased the HO-8910-G cell migration potential and tumor metastasis. Collectively, our study indicated that HLA-G involved in tumor invasiveness or metastasis may rely on the NK cytotoxicity inhibition and induction of MMP-15 expression in ovarian cancer.
AuthorsAifen Lin, Hui-Hui Xu, Dan-Ping Xu, Xia Zhang, Qing Wang, Wei-Hua Yan
JournalHuman immunology (Hum Immunol) Vol. 74 Issue 4 Pg. 439-46 (Apr 2013) ISSN: 1879-1166 [Electronic] United States
PMID23228395 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
Chemical References
  • HLA-G Antigens
  • RNA, Small Interfering
  • Matrix Metalloproteinase 15
Topics
  • Animals
  • Carcinoma (genetics, immunology, pathology)
  • Cell Line, Tumor
  • Cell Movement
  • Cytotoxicity, Immunologic
  • Female
  • Gene Expression Regulation, Neoplastic (immunology)
  • HLA-G Antigens (genetics, immunology)
  • Humans
  • Killer Cells, Natural (immunology, pathology)
  • Matrix Metalloproteinase 15 (genetics, immunology)
  • Mice
  • Mice, Nude
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Ovarian Neoplasms (genetics, immunology, pathology)
  • RNA, Small Interfering

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