This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Miyata, Y. Articles by Kanda, S. Search for Related Content PubMed PubMed Citation Articles by Miyata, Y. Articles by Kanda, S.

Expression of Thrombospondin-derived 4N1K Peptide-containing Proteins in Renal Cell Carcinoma Tissues Is Associated with a Decrease in Tumor Growth and Angiogenesis¹

Department of Urology [Y. M., S. Ko., K. T., H. K., S. Ka.] and Department of Molecular Microbiology and Immunology, Division of Endothelial Cell Biology [S. Ka.], Nagasaki University Graduate School of Medical Science, Nagasaki 852-8501, Japan

Purpose: We have reported that the 4N1K peptide (KRFYVVMWKK) from thrombospondin (TSP) 1 has antiangiogenic activities. The goal of this study was to examine whether the expression of 4N1K-containing proteins correlates with reduced growth of human renal cell carcinoma (RCC).

Experimental Design: We examined the expression of 4N1K-containing proteins and TSP1, microvessel density, proliferation index, and apoptotic index in 119 surgically excised RCC tissues by immunohistochemical techniques. The correlation between the above variables and clinicopathological features was analyzed statistically.

Results: The antibody raised against the 4N1K peptide recognized protein fragments of matrix metalloproteinase 3-digested TSP1 and positively stained the sections of renal cancer tissues. These reactions disappeared when the antibody was preincubated with immobilized 4N1K peptide, suggesting that the reactions were 4N1K peptide specific. Although TSP1 expression did not correlate with various clinicopathological features and tumor size, all 4N1K-positive tumors were locally confined and of significantly smaller size (median, 3.3 cm; range, 2.0–4.4 cm) than 4N1K-negative tumors (median, 5.2 cm; range, 2.8–8.8 cm; P < 0.001). 4N1K-positive tumors exhibited significantly lower microvessel density and higher apoptotic index of tumor cells than 4N1K-negative tumors (P < 0.001 and P = 0.042, respectively).

Conclusions: Our data suggest that expression of 4N1K-containing proteins in tumor tissues is associated with reduced angiogenesis and tumor growth; thus, it would be a potentially predictive marker for progression of RCC.

This article has been cited by other articles:

				Y.-W. Zhang, Y. Su, O. V. Volpert, and G. F. V. Woude Hepatocyte growth factor/scatter factor mediates angiogenesis through positive VEGF and negative thrombospondin 1 regulation PNAS, October 28, 2003; 100(22): 12718 - 12723. [Abstract] [Full Text] [PDF]