Gene expression profiling of the tumor microenvironment during breast cancer progression
By Xiao-Jun Ma, S. Dahiya, E. Richardson, M. Erlander, D. Sgroi. Breast Cancer Research, 2009
629 citations recorded by the source corpus.
IntroductionThe 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.MethodsWe 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.ResultsTumor-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.ConclusionsOur 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.
Subfields: Cancer Research, Immunology and Allergy, Oncology
View Paper: https://www.semanticscholar.org/paper/aa76b6abc50715a49c4166c06e7f5061ae59b47b
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Citations in the corpus
- Fibroblast Heterogeneity and Immunosuppressive Environment in Human Breast Cancer. (2018, neutral): “Several gene expression signatures have been tested in the past to appreciate stromal composition (Chang et al., 2005; Finak et al., 2008; Ma et al., 2009; Planche et al., 2011; Desmedt et al., 2012; Frings et al., 2013; Guo et al., 2013).”
- Prognostic significance of the tumor-stroma ratio: validation study in node-negative premenopausal breast cancer patients from the EORTC perioperative chemotherapy (POP) trial (10854) (2013, background): “Gene expression array data have shown that the activation of tumor-stroma begins relatively early in the process of tumor development, even when the tumor epithelium is pre-invasive [3].”