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Title: Microenvironmental control of breast cancer subtype elicited through paracrine platelet-derived growth factor-CC signaling.
Austin Authors: Roswall, Pernilla;Bocci, Matteo;Bartoschek, Michael;Li, Hong;Kristiansen, Glen;Jansson, Sara;Lehn, Sophie;Sjölund, Jonas;Reid, Steven;Larsson, Christer;Eriksson, Pontus;Anderberg, Charlotte;Cortez, Eliane;Saal, Lao H;Orsmark-Pietras, Christina;Cordero, Eugenia;Haller, Bengt Kristian;Häkkinen, Jari;Burvenich, Ingrid J G;Lim, Elgene;Orimo, Akira;Höglund, Mattias;Rydén, Lisa;Moch, Holger;Scott, Andrew M ;Eriksson, Ulf;Pietras, Kristian
Affiliation: Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden
University of New South Wales, Sydney, New South Wales, Australia
Garvan Institute of Medical Research, Sydney, New South Wales, Australia
Institute of Pathology, University Hospital Bonn, Bonn, Germany
Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden
Division of Vascular Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden
Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo, Japan
Department of Pathology and Molecular Pathology, University Hospital Zürich, Zürich, Switzerland
School of Cancer Medicine, La Trobe University, Melbourne, Victoria, Australia
Issue Date: May-2018
Date: 2018-05-12
Publication information: Nature medicine 2018; 24(4): 463-473
Abstract: Breast tumors of the basal-like, hormone receptor-negative subtype remain an unmet clinical challenge, as there is high rate of recurrence and poor survival in patients following treatment. Coevolution of the malignant mammary epithelium and its underlying stroma instigates cancer-associated fibroblasts (CAFs) to support most, if not all, hallmarks of cancer progression. Here we delineate a previously unappreciated role for CAFs as determinants of the molecular subtype of breast cancer. We identified paracrine crosstalk between cancer cells expressing platelet-derived growth factor (PDGF)-CC and CAFs expressing the cognate receptors in human basal-like mammary carcinomas. Genetic or pharmacological intervention of PDGF-CC activity in mouse models of cancer resulted in conversion of basal-like breast cancers into a hormone receptor-positive state that enhanced sensitivity to endocrine therapy in previously resistant tumors. We conclude that specification of breast cancer to the basal-like subtype is under microenvironmental control and is therapeutically actionable.
DOI: 10.1038/nm.4494
ORCID: 0000-0002-0815-1896
Journal: Nature medicine
PubMed URL: 29529015
Type: Journal Article
Appears in Collections:Journal articles

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