Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Vascular properties of breast cancer intrinsic subtypes

ABSTRACT: Interactions of cancer cells with the vasculature are essential for tumor growth and likely promote metastatic progression. Endothelial cell content and lympho-vascular invasion are generally associated with tumor aggressiveness, however, these features are generally not employed in the clinic. We aimed to determine if endothelial cell gene expression signatures could be utilized to better characterize breast tumor biology, and to establish if vascular cell-derived signatures could provide information to predict tumors likely to metastasize. Here we report on the identification of a gene signature for vascular endothelial cells, and a second for cancer-activated vasculature. Both signatures independently identify subsets of aggressive breast cancers. Interestingly, the vascular content signature and a previously identified hypoxia signature both provide prognostic information beyond currently utilized clinical parameters and intrinsic subtype classifications. In these studies, we also examined the relationship that the breast cancer subtypes have with vascular gene expression profiles, and found that claudin-low tumors and cell lines express vascular gene expression profiles and displayed endothelial-like tube formation when grown in three-dimensions. These findings are directly applicable to clinical care and therapeutic treatment design as they identify highly aggressive subsets of tumors with genetic and morphologic vascular properties. reference x sample

ORGANISM(S): Homo sapiens

SUBMITTER: Charles Perou

PROVIDER: E-GEOD-37145 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Endothelial-like properties of claudin-low breast cancer cells promote tumor vascular permeability and metastasis.

Harrell J Chuck JC Pfefferle Adam D AD Zalles Nicole N Prat Aleix A Fan Cheng C Khramtsov Andrey A Olopade Olufunmilayo I OI Troester Melissa A MA Dudley Andrew C AC Perou Charles M CM

Clinical & experimental metastasis 20130822 1

The vasculature serves as the main conduit for breast tumor metastases and is a target of therapeutics in many tumor types. In this study, we aimed to determine if tumor-associated vascular properties could help to explain the differences observed in metastagenicity across the intrinsic subtypes of human breast tumors. Analysis of gene expression signatures from more than 3,000 human breast tumors found that genomic programs that measured vascular quantity, vascular proliferation, and a VEGF/Hyp ...[more]

PMID: 23975155

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Project description:Introduction: Over the past several years, we have been interested in understanding the mechanisms by which hormone-dependent (HD) mammary carcinomas grow in the absence of the stimulatory hormone. We have hypothesized that the stromal compartment plays a pivotal role in the acquisition of the hormone-independent (HI) phenotype by providing stimulatory factors that replace the proliferative effects of the hormone. Methods: We used DNA microarrays to compare the gene expression profiles of tumors from the MPA mouse breast cancer model, one hormone-dependent (C4-HD) and one hormone-independent (C4-HI), using whole tumor samples or laser-captured purified stromal and epithelial cells obtained from the same tumors. The expression of selected genes was validated by immunohistochemistry and immunofluorescence assays. Results: We identified 413 genes that were expressed in tumor stroma but not in epithelial cells. Eighty-five percent of these genes were upregulated, whereas the remaining 15% were downregulated in C4-HI tumors relative to their expression in the C4-HD tumor stroma. Several matrix metallopeptidases, including Mmp13, Mmp3, Mmp10 and Mmp9, were overexpressed in the C4-HI tumor microenvironment. On the other hand, 1100 genes were specifically expressed in the tumor parenchyma. Among them, the 29% were upregulated, whereas the remaining 71% were downregulated, in C4-HI relative to C4-HD tumor epithelium. Steap, Pdgfc, Runx2, Cxcl9 and Sdf2 were among the genes with high expression in the C4-HI tumor parenchyma. Interestingly, we found that Fgf2 was one of the few genes upregulated by MPA in C4-HD tumors, confirming its pivotal role in regulating tumor growth in this model. Conclusions: We demonstrate a gene expression profile that distinguishes epithelial from stromal cells in mammary tumors with different hormone dependence. Our results support the hypothesis that the tumor-associated stroma may contribute to hormone-independent tumor growth. The fact that Fgf2 was one of these few stimulatory genes is worth investigating. reference X sample

Dataset Information

Vascular properties of breast cancer intrinsic subtypes

Publications

Endothelial-like properties of claudin-low breast cancer cells promote tumor vascular permeability and metastasis.

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