Association of matrix metalloproteinase-9 and decorin expression with the infiltration of cervical cancer.

Abstract

Matrix metalloproteinase-9 (MMP9) has been recognized to be an important factor in cancer invasion and metastasis. In contrast, decorin has been revealed to inhibit primary tumor development. The aim of the present study was to investigate the function of MMP9 and decorin in cervical cancer. Three experiments were performed to analyze the function of MMP9 and decorin in the invasion of cervical cancer by: i) Analyzing the expression of MMP9 and decorin by immunohistochemistry in 100 cervical specimens; ii) determining the concentration of decorin by an enzyme-linked immunosorbent assay (ELISA) using the human squamous cervical cancer cell line CaSki and human endometrial stromal cell line CRL4003 and iii) evaluating the invasion ability of CaSki cells in a cervical invasion model by an invasion assay. Immunohistochemistry revealed that MMP9 was overexpressed in microinvasive carcinoma (100.0%) but was less strongly expressed in normal or pre-malignant squamous epithelium (0-41.9%). In contrast, the activity of decorin in stroma adjacent to neoplastic cells was lower in microinvasive carcinoma (9.1%) compared with in normal or pre-malignant lesions (74.2-100.0%). An ELISA revealed that MMP9 released from CaSki cells resolved the decorin released from CRL4003 cells. An invasion assay demonstrated that the invasive ability of CaSki cells was suppressed by an MMP inhibitor, and decorin was released from CRL4003 cells. These data suggested that decorin prevented the invasion of malignant cells in uterine cervical cancer; however, MMP9 promotes cell invasion by destroying decorin.