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

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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.

In: Nature Medicine, Vol. 24, 12.03.2018, p. 463–473.

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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. / Microenvironmental control of breast cancer subtype elicited through paracrine platelet-derived growth factor-CC signaling. In: Nature Medicine. 2018 ; Vol. 24. pp. 463–473.

RIS

TY - JOUR

T1 - Microenvironmental control of breast cancer subtype elicited through paracrine platelet-derived growth factor-CC signaling

AU - Roswall, Pernilla

AU - Bocci, Matteo

AU - Bartoschek, Michael

AU - Li, Hong

AU - Kristiansen, Glen

AU - Jansson, Sara

AU - Lehn, Sophie

AU - Sjölund, Jonas

AU - Reid, Steven

AU - Larsson, Christer

AU - Eriksson, Pontus

AU - Anderberg, Charlotte

AU - Cortez, Eliane

AU - Saal, Lao H

AU - Orsmark-Pietras, Christina

AU - Cordero, Eugenia

AU - Haller, Bengt Kristian

AU - Häkkinen, Jari

AU - Burvenich, Ingrid J G

AU - Lim, Elgene

AU - Orimo, Akira

AU - Höglund, Mattias

AU - Rydén, Lisa

AU - Moch, Holger

AU - Scott, Andrew M

AU - Eriksson, Ulf

AU - Pietras, Kristian

PY - 2018/3/12

Y1 - 2018/3/12

N2 - 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.

AB - 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.

U2 - 10.1038/nm.4494

DO - 10.1038/nm.4494

M3 - Article

VL - 24

SP - 463

EP - 473

JO - Nature Medicine

T2 - Nature Medicine

JF - Nature Medicine

SN - 1546-170X

ER -