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

Authors
Journal
Human Immunology
0198-8859
Publisher
Elsevier
Volume
74
Issue
4
Identifiers
DOI: 10.1016/j.humimm.2012.11.021
Disciplines
  • Biology
  • Engineering
  • Medicine

Abstract

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.

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