Expression of Matrix Metalloproteinase-7 on Cancer Cells and Tissue Endothelial Cells in Renal Cell Carcinoma: Prognostic Implications and Clinical Significance for Invasion and Metastasis

Abstract

Purpose: The expression of matrix metalloproteinase-7 (MMP-7) correlates with the malignant potential of various tumors and patient survival.We investigated the clinical and prognostic significance of MMP-7 expression in cancer cells and endothelial cells in human renal cell carcinoma (RCC). Experimental Design: We reviewed tissue samples of 156 patients with RCC who had undergone radical operation. MMP-7 expression was examined by immunohistochemistry. Sections containing MMP-7-positive vessels were also stained for CD34. The density of MMP-7-positive vessels was determined by a computer-aided image analysis system. Multivariate analysis was done to assess relevant variables for invasion, metastasis, and cause-specific survival.Results: The proportion of MMP-7-expressing tumor cells were significantly higher (P < 0.001) than that of normal cells. MMP-7-positive vessels were considered blood vessels based on staining for CD34, and their density was increased in tumor areas. The proportion of MMP-7-expressing cancer cells and density of MMP-7-positive vessels correlated with grade, pathologic tumor stage, and metastasis. Multivariate analysis showed that MMP-7 expression on cancer cells correlated with pathologic tumor stage only, whereas MMP-7-positive vessel density correlated with metastasis only. The elevated status of MMP-7 in cancer tissues was an independent predictor for cause-specific survival (odds ratio, 8.61; P = 0.040) by multivariate analysis. Conclusions: Our results showed that MMP-7 influences tumor progression by regulating invasion and angiogenesis. Multivariate analysis showed that MMP-7 status of cancer tissues was strong predictor of poor prognosis. Our results suggest that MMP-7 targeting treatment may be a potential target against RCC. Systemic dissemination of cancer cells influences prognosis inthe majority of malignancies. Many factors are associated with this process, and cancer cell invasion into surrounding tissue is one of the early and crucial steps. In addition, the formation of new capillaries (neoangiogenesis) is also an important process in tumor growth and metastasis in solid tumors (1, 2). Degradation of the extracellular matrix and destruction of the basement membrane by cancer cells are important processes for direct invasion. Likewise, degradation of extracellular matrix of endothelial cells is one of the initial steps in neoangiogenesis. Thus, these processes are important for tumor progression and prognosis, and full understanding is essential in the planning of treatment and observation strategy.Matrix metalloproteinases (MMP) are zinc-dependent proteolytic enzymes capable of cleaving extracellular matrix components. Several investigators have paid special attention to the pathologic significance of MMPs in cancer cells, and it is a well-known fact that MMPs are overexpressed in a variety of cancers and play important roles in cancer invasion and metastasis (3 -5). In addition to cancer cells, several investigators found that some MMPs are secreted by endotheli...

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Carcinogenesis of renal cell carcinoma reflected in HLA ligands: A novel approach for synergistic peptide vaccination design

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