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Microenvironmental control of breast cancer subtype elicited through paracrine platelet-derived growth factor-CC signaling.
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.
Afiliación
  • Roswall P; Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden.
  • Bocci M; Division of Vascular Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
  • Bartoschek M; Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden.
  • Li H; Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden.
  • Kristiansen G; Division of Vascular Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
  • Jansson S; Institute of Pathology, University Hospital Bonn, Bonn, Germany.
  • Lehn S; Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden.
  • Sjölund J; Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden.
  • Reid S; Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden.
  • Larsson C; Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden.
  • Eriksson P; Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden.
  • Anderberg C; Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden.
  • Cortez E; Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden.
  • Saal LH; Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden.
  • Orsmark-Pietras C; Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden.
  • Cordero E; Division of Clinical Genetics, Department of Laboratory Medicine, Lund University, Lund, Sweden.
  • Haller BK; Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, Sweden.
  • Häkkinen J; Division of Vascular Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
  • Burvenich IJG; Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden.
  • Lim E; Olivia Newton-John Cancer Research Institute and School of Cancer Medicine, La Trobe University, Melbourne, Victoria, Australia.
  • Orimo A; Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
  • Höglund M; University of New South Wales, Sydney, New South Wales, Australia.
  • Rydén L; Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo, Japan.
  • Moch H; Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden.
  • Scott AM; Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden.
  • Eriksson U; Department of Pathology and Molecular Pathology, University Hospital Zürich, Zürich, Switzerland.
  • Pietras K; Olivia Newton-John Cancer Research Institute and School of Cancer Medicine, La Trobe University, Melbourne, Victoria, Australia.
Nat Med ; 24(4): 463-473, 2018 05.
Article en En | MEDLINE | ID: mdl-29529015
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Factor de Crecimiento Derivado de Plaquetas / Linfocinas / Comunicación Paracrina / Microambiente Tumoral Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans / Middle aged Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2018 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Factor de Crecimiento Derivado de Plaquetas / Linfocinas / Comunicación Paracrina / Microambiente Tumoral Tipo de estudio: Prognostic_studies Límite: Animals / Female / Humans / Middle aged Idioma: En Revista: Nat Med Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA Año: 2018 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Estados Unidos