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

Content Provider	Springer Nature Link
Author	Harrell, J. Chuck Pfefferle, Adam D. Zalles, Nicole Prat, Aleix Fan, Cheng Khramtsov, Andrey Olopade, Olufunmilayo I. Troester, Melissa A. Dudley, Andrew C. Perou, Charles M.
Copyright Year	2013
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.
Starting Page	33
Ending Page	45
Page Count	13
File Format	PDF
ISSN	02620898
Journal	Clinical & Experimental Metastasis
Volume Number	31
Issue Number	1
e-ISSN	15737276
Language	English
Publisher	Springer Netherlands
Publisher Date	2013-08-22
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Angiogenesis Breast cancer Gene signature Metastasis Microarray Cancer Research Biomedicine general Oncology Hematology Surgical Oncology
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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

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