Heterogeneous perivascular cell coverage affects breast cancer metastasis and response to chemotherapy

Heterogeneous perivascular cell coverage affects breast cancer metastasis and response to chemotherapy

Author Kim, Jiha Google Scholar
de Sampaio, Pedro Correa Google Scholar
Lundy, Donna Marie Google Scholar
Peng, Qian Google Scholar
Evans, Kurt W. Google Scholar
Sugimoto, Hikaru Google Scholar
Gagea, Mihai Google Scholar
Kienast, Yvonne Google Scholar
do Amaral, Nayra Soares Google Scholar
Rocha, Rafael Malagoli Autor UNIFESP Google Scholar
Eikesdal, Hans Petter Google Scholar
Lonning, Per Eystein Google Scholar
Meric-Bernstam, Funda Google Scholar
LeBleu, Valerie S. Google Scholar
Abstract Angiogenesis and co-optive vascular remodeling are prerequisites of solid tumor growth. Vascular heterogeneity, notably perivascular composition, may play a critical role in determining the rate of cancer progression. The contribution of vascular pericyte heterogeneity to cancer progression and therapy response is unknown. Here, we show that angiopoietin-2 (Ang2) orchestrates pericyte heterogeneity in breast cancer with an effect on metastatic disease and response to chemotherapy. Using multispectral imaging of human breast tumor specimens, we report that perivascular composition, as defined by the ratio of PDGFR beta(-) and desmin(+) pericytes, provides information about the response to epirubicin but not paclitaxel. Using 17 distinct patient-derived breast cancer xenografts, we demonstrate a cancer cell-derived influence on stromal Ang2 production and a cancer cell-defined control over tumor vasculature and perivascular heterogeneity. The aggressive features of tumors and their distinct response to therapies may thus emerge by the cancer cell-defined engagement of distinct and heterogeneous angiogenic programs.
xmlui.dri2xhtml.METS-1.0.item-coverage Ann Arbor
Language English
Sponsor NIH [CA155370]
University of Texas Faculty Science and Technology Acquisition and Retention (STARs) Program
NIH/National Cancer institute Cancer Center Support Grant New Faculty Award [P30CA016672]
UT MD Anderson Cancer Center through the Khalifa Bin Zayed Al Nahyan Foundation
Helse Vest
Bergen Medical Research Foundation
Norwegian Cancer Society
Rieber Foundation, Norway
Date 2016
Published in Jci Insight. Ann Arbor, v. 1, n. 21, p. -, 2016.
ISSN 2379-3708 (Sherpa/Romeo, impact factor)
Publisher Amer Soc Clinical Investigation Inc
Extent -
Origin http://dx.doi.org/10.1172/jci.insight.90733
Access rights Closed access
Type Article
Web of Science ID WOS:000392963700010
URI https://repositorio.unifesp.br/handle/11600/56537

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