4324

MMP15

matrix metallopeptidase 15 (membrane-inserted);MMP15;matrix metallopeptidase 15 (membrane-inserted)

MMP-15|MT-MMP 2|MT2MMP|matrix metalloproteinase 15 (membrane-inserted)|matrix metalloproteinase-15|membrane-type matrix metalloproteinase 2|membrane-type-2 matrix metalloproteinase

16q13

protein-coding

OBJECTIVE: To construct differential expression profiles of adenoid cystic carcinoma cell lines for screening candidate genes related to metastasis and to verify some candidate genes in adenoid cystic carcinoma. METHODS: Restriction fragments differential display PCR (RFDD-PCR) was used to set up gene expression profiles of adenoid cystic carcinoma cell lines-ACC-M and ACC-2, with high and low metastasis potential respectively. Candidate genes were screened through bioinformatics analysis. Then, a gene family of these candidate genes was checked using semi-quantitative reverse transcription-PCR(RT-PCR). RESULTS: Two gene expression profiles including 5420 gene fragments were constructed, 12 genes of a family called matrix metalloproteinase genes (MMPs) were observed obvious differentially expressed between two cell lines. Results of semi-quantitative RT-PCR also identified this different expression of MMP2,MMP7,MMP9,MMP14,MMP15 and MMP24. CONCLUSION: The construction of gene expression profiles of ACC-M and ACC-2 cell lines makes the foundation for seeking the target genes of adenoid cystic carcinoma. MMP2,MMP7,MMP9 and MMP15 may be relevant with carcinogenesis, development and metastasis of adenoid cystic carcinoma, and different metastasis potential may result from different subtype of MMPs gene family.

PURPOSE: To analyze the behavior of matrix metalloproteinases (MMPs) in their active state in patients with bladder cancer. METHOD: A retrospective study of 50 patients with localized bladder cancer who underwent tumor resection between June 2006 and June 2007 at the National cancer Institute in Cairo, Egypt was carried out. Tissue samples were collected and the expression of membrane type 1 (MT1) and type 2 (MT2) MMPs was determined by Western blotting. Gelatinase A (MMP-2) activity was estimated by zymographic analysis in tissue samples of each patient and the values were correlated with clinical tumor stage and lymph node status. RESULT: The behavior of MMP-2 showed statistical significance in 90% of tumor tissues compared with 22% of adjacent normal tissues (p<0.001). MT1-MMP was expressed in 88% of tumor tissues compared with 24% of normal tissues (p<0.001); MT2-MMP was expressed in 74% of tumor tissues compared with 12% of normal tissues (p<0.001). While there was a highly significant association between MMP-2 activity and MT1-MMP expression in tumor tissues (p<0.001), there was a moderately significant association between MMP-2 activity and MT2-MMP expression (p=0.018). The results also revealed an association between MT1-MMP and MT2-MMP expression in tumor tissues (p<0.001). MMP-2 activity and MT2-MMP expression in tumor tissues were statistically associated with high tumor stage (p=0.039 and p=0.014, respectively), while the expression of MT1-MMP showed no association with tumor stage (p=0.139). CONCLUSION: MMP-2 activity is associated with an increase in MT2-MMP expression and with lymph node metastasis. No association was found between MT1-MMP expression and lymph node metastasis.

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.