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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Pernilla Roswall
  • Hong Li
  • Glen Kristiansen
  • Charlotte Anderberg
  • Eliane Cortez
  • Eugenia Cordero
  • Bengt Kristian Haller
  • Ingrid J G Burvenich
  • Elgene Lim
  • Akira Orimo
  • Holger Moch
  • Andrew M Scott
  • Ulf Eriksson
Organisations
External organisations
  • University of New South Wales
  • University Hospital of Zurich
  • Karolinska Institutet
  • Universitätsklinikum Bonn
  • Lund University
  • La Trobe University
  • Juntendo University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
Original languageEnglish
Pages (from-to)463–473
JournalNature Medicine
Volume24
Publication statusPublished - 2018 Mar 12
Publication categoryResearch
Peer-reviewedYes

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