Enhanced peritoneal ovarian tumor dissemination by tissue transglutaminase

Minati Satpathy, Liyun Cao, Roxana Pincheira, Robert Emerson, Robert Bigsby, Harikrishna Nakshatri, Daniela Matei*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

80 Scopus citations

Abstract

Tissue transglutaminase (TG2) is involved in Ca2+-dependent aggregation and polymerization of proteins. We previously reported that TG2 mRNA is up-regulated in epithelial ovarian cancer (EOC) cells compared with normal ovarian epithelium. Here, we show overexpression of the TG2 protein in ovarian cancer cells and tumors and its secretion in ascites fluid and define its role in EOC. By stable knockdown and overexpression, we show that TG2 enhances EOC cell adhesion to fibronectin and directional 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 knockdown diminishes dissemination of tumors on the peritoneal surface and mesentery in an i.p. ovarian xenograft model. This phenotype is associated with deficient β1 integrin-fibronectin interaction, leading to weaker anchorage of cancer cells to the peritoneal matrix. Highly expressed in ovarian tumors, TG2 facilitates i.p. tumor dissemination by enhancing cell adhesion to the extracellular matrix and modulating β1 integrin subunit expression.

Original languageEnglish (US)
Pages (from-to)7194-7202
Number of pages9
JournalCancer Research
Volume67
Issue number15
DOIs
StatePublished - Aug 1 2007

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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