Accession Number:

ADA478840

Title:

Regulation of Leukocyte Infiltration into Ovarian Cancer by Tumor-Stroma Interactions, a Microarray View of Cancer Microenvironment

Descriptive Note:

Final rept. 1 Mar 2004-28 Feb 2007

Corporate Author:

MELBOURNE UNIV VICTORIA (AUSTRALIA)

Report Date:

2007-03-01

Pagination or Media Count:

59.0

Abstract:

Despite compelling cell biological studies and histopathological observations incriminating stromal cells in tumorigenesis, our knowledge of the genes that mediate changes in the tumor microenvironment and interactions among various cell types in epithelial cancer and their role in tumorigenesis is limited. Here, we describe a comprehensive molecular characterization of stromal-epithelial cell interactions, using microarray analysis of co-cultured cell pairs. We further show that these gene expression changes indeed are common feature of in vivo profiles of invasive epithelial cancers. Using In situ hybridization and laser capture microdissection, we confirmed previous assignment of which cells express which genes in response to co-culture. We provide proof of principle evidence that the in vitro system recapitulates some aspects of cancer cell biology and may contribute new markers to the invasive events. We directly demonstrate that events in the interaction of epithelial cells and their neighboring fibroblasts play initial role in recruiting inflammatory cells and provoking immune surveillance. We found the Epithelial-to-Mesenchymal Transition of the cancer cells shRNA-mediated E-Cadherin knock down attenuates the co-culture reaction, suggesting a mechanism for cancer cell evasion of immune surveillance.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE