MATERIALS AND METHODS FOR DETECTING AND TREATING PERITONEAL OVARIAN TUMOR DISSEMINATION INVOLVING TISSUE TRANSGLUTAMINASE

摘要

Tissue transglutaminase (TG2) is involved in Ca⁺⁺-dependent aggregation and polymerization of proteins. TG2 is upregulated in epithelial ovarian cancer (EOC) cells as compared to normal ovarian epithelium. TG2 is also highly expressed in ovarian tumors and secreted in malignant ascites, but it is not detected in non-transformed ovarian epithelium. Furthermore, TG2 enhances EOC cell adhesion to fibronectin and haptotactic cell migration. This phenotype is preserved in-vivo, where the pattern of tumor dissemination in the peritoneal space is dependent on TG2 expression levels. TG2 knock down diminishes dissemination of tumors on the peritoneal surface and mesentery in an i.p. ovarian xenograft model. This phenotype is due to deficient ßl integrin- fibronectin interaction, leading to weaker anchorage of cancer cells to the peritoneal matrix. Highly expressed in ovarian tumors, TG2 facilitates intra¬ peritoneal tumor dissemination, by enhancing cell adhesion to the extracellular matrix and modulating ßl integrin subunit expression. Accordingly, high levels of TGL activity is implicate in the dissemination ovarian cancer cells. Methods for diagnosing and monitoring ovarian cancers include assessing the level of TG2 and activity. Materials and methods for detecting, preventing and/or treating peritoneal metastasis of ovarian cancers including measuring the level and or activity of TG2 and/or administering compounds that regulate the level and/or activity of TG2.