Microenvironmental control of breast cancer subtype elicited through paracrine platelet-derived growth factor-CC signaling

Research output: Contribution to journalArticle


title = "Microenvironmental control of breast cancer subtype elicited through paracrine platelet-derived growth factor-CC signaling",
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.",
author = "Pernilla Roswall and Matteo Bocci and Michael Bartoschek and Hong Li and Glen Kristiansen and Sara Jansson and Sophie Lehn and Jonas Sj{\"o}lund and Steven Reid and Christer Larsson and Pontus Eriksson and Charlotte Anderberg and Eliane Cortez and Saal, {Lao H} and Christina Orsmark-Pietras and Eugenia Cordero and Haller, {Bengt Kristian} and Jari H{\"a}kkinen and Burvenich, {Ingrid J G} and Elgene Lim and Akira Orimo and Mattias H{\"o}glund and Lisa Ryd{\'e}n and Holger Moch and Scott, {Andrew M} and Ulf Eriksson and Kristian Pietras",
year = "2018",
month = "3",
day = "12",
doi = "10.1038/nm.4494",
language = "English",
volume = "24",
pages = "463–473",
journal = "Nature Medicine",
issn = "1546-170X",
publisher = "Nature Publishing Group",