Abstract
Little is known about the phenotypic changes that lead to malignant transformation in human sarcomas. Previously, we have demonstrated that epithelial malignancies overexpress the novel TSP-1 receptor, angiocidin. We now hypothesize that a malignant phenotype results in overexpression of angiocidin in human sarcomas. Methods. Angiocidin and TSP-1 expression were determined in 10 human sarcomas by immunohistochemistry (IHC). Additionally, we established three cell lines from a patient with an osteosarcoma: EXOS-N (normal mesenchymal cell line), EXOS-P (primary osteosarcoma cell line), and EXOS-M (lung metastasis cell line). Extensive comparative gene expression in all three lines was performed by DNA microarray analysis using the Affymetrix U74Av2 array with probes for 12,500 genes. Angiocidin and TSP-1 expression in all three cell lines were determined by Western blot, IHC, and immunofluorescence. Results. IHC on human sarcomas showed overexpression of angiocidin and TSP-1 on tumor cells and tumor-associated stroma. Minimal expression was observed in normal tissues. Comparative gene analysis on the three different cell lines by DNA microarray analysis showed that angiocidin and TSP-1 gene expression was negligible in EXOS-N cells, high in EXOS-P cells, and highest in EXOS-M cells. Angiocidin and TSP-1 protein expression was similarly minimal in EXOS-N cells, higher in EXOS-P cells, and highest in EXOS-M cells as demonstrated by Western blot (Figures 1 and 2) and confirmed by IHC and immunofluorescence. Conclusion. Angiocidin and TSP-1 expression correlate with a malignant phenotype in human sarcomas. Furthermore, overexpression of angiocidin and TSP-1 may lead to the acquisition of a metastatic phenotype.
Published Version
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