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Breast Cancer Research
Published in: Breast Cancer Research 1/2009

Open Access 01-06-2009 | Research article

Gene expression profiling of the tumor microenvironment during breast cancer progression

Authors: Xiao-Jun Ma, Sonika Dahiya, Elizabeth Richardson, Mark Erlander, Dennis C Sgroi

Published in: Breast Cancer Research | Issue 1/2009

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Abstract

Introduction

The importance of the tumor microenvironment in breast cancer has been increasingly recognized. Critical molecular changes in the tumor stroma accompanying cancer progression, however, remain largely unknown. We conducted a comparative analysis of global gene expression changes in the stromal and epithelial compartments during breast cancer progression from normal to preinvasive to invasive ductal carcinoma.

Methods

We combined laser capture microdissection and gene expression microarrays to analyze 14 patient-matched normal epithelium, normal stroma, tumor epithelium and tumor-associated stroma specimens. Differential gene expression and gene ontology analyses were performed.

Results

Tumor-associated stroma undergoes extensive gene expression changes during cancer progression, to a similar extent as that seen in the malignant epithelium. Highly upregulated genes in the tumor-associated stroma include constituents of the extracellular matrix and matrix metalloproteases, and cell-cycle-related genes. Decreased expression of cytoplasmic ribosomal proteins and increased expression of mitochondrial ribosomal proteins were observed in both the tumor epithelium and the stroma. The transition from preinvasive to invasive growth was accompanied by increased expression of several matrix metalloproteases (MMP2, MMP11 and MMP14). Furthermore, as observed in malignant epithelium, a gene expression signature of histological tumor grade also exists in the stroma, with high-grade tumors associated with increased expression of genes involved in immune response.

Conclusions

Our results suggest that the tumor microenvironment participates in tumorigenesis even before tumor cells invade into stroma, and that it may play important roles in the transition from preinvasive to invasive growth. The immune cells in the tumor stroma may be exploited by the malignant epithelial cells in high-grade tumors for aggressive invasive growth.
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Metadata
Title
Gene expression profiling of the tumor microenvironment during breast cancer progression
Authors
Xiao-Jun Ma
Sonika Dahiya
Elizabeth Richardson
Mark Erlander
Dennis C Sgroi
Publication date
01-06-2009
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2009
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr2222

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