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Title: Endothelial-like properties of claudin-low breast cancer cells promote tumor vascular permeability and metastasis
Author: Harrell, J. C.
Pfefferle, A. D.
Zalles, N.
Prat Aparicio, Aleix
Fan, C.
Khramtsov A
Olopade, O. I.
Troester, M. A.
Dudley. A. C.
Perou, C. M.
Keywords: Càncer de mama
Microxips d'ADN
Breast cancer
DNA microarrays
Issue Date: 15-Jan-2014
Publisher: Springer Verlag
Abstract: 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/Hypoxia-signature were the most highly expressed in claudin-low and basal-like tumors. The majority of the vascular gene signatures added metastasis-predictive information to immunohistochemistry-defined microvessel density scores and genomically defined-intrinsic subtype classification. Interestingly, pure claudin-low cell lines, and subsets of claudin-low-like cells within established basal-like cancer cell lines, exhibited endothelial/tube-like morphology when cultured on Matrigel. In vivo xenografts found that claudin-low tumors, but not luminal tumors, extensively perfused injected contrast agent through paracellular spaces and non-vascular tumor-lined channels. Taken together, the endothelial-like characteristics of the cancer cells, combined with both the amount and the physiologic state of the vasculature contribute to breast cancer metastatic progression. We hypothesize that the genetic signatures we have identified highlight patients that should respond most favorably to anti-vascular agents.
Note: Reproducció del document publicat a:
It is part of: Clinical & Experimental Metastasis, 2014, vol. 31, num. 1, p. 33-45
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ISSN: 0262-0898
Appears in Collections:Articles publicats en revistes (Medicina)

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