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MedicineAnatomy and Physiology

Regulation of Leukocyte Infiltration into Ovarian Cancer by Tumour-Stroma Interactions; A Microarray View of Cancer Microenvironment

Authors: Izhak Haviv; PETER MACCALLUM CANCER INST MELBOURNE (AUSTRALIA)
Abstract:
The focus: 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. 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. A reverse signal transduction approach: Perhaps the biggest innovation lies in the demonstrated ability to discern cytokine molecules that provoke the gene expression in the co-culture. This in turn provides new working hypotheses to test in vivo, on the etiological role of particular molecules in dictating the clinical course of the disease.

Limitations: APPROVED FOR PUBLIC RELEASE
Description: Annual rept. 1 Mr 2004-28 Feb 2005
Pages: 22
Report Date: MAR 2005
Contract Number: W81XWH0410336
Report Number: A679344
Keywords relating to this report:
*OVARIAN CANCER
CANCER
CELLS
CYTOKINES
EPITHELIUM
ETIOLOGY
FIBROBLASTS
GENES
HISTOPATHOLOGY
HYPOTHESES
IMMUNITY
IN VITRO ANALYSIS
IN VIVO ANALYSIS
INFILTRATION_FLUIDS_
INFLAMMATION
LEUKOCYTES
MARKERS
MOLECULES
NEOPLASMS
PRODUCTION
PROFILES
REVERSIBLE
SIGNALS
SURVEILLANCE
TEST AND EVALUATION
TRANSDUCERS
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