Microenvironmental Control of Breast Cancer Subtype Elicited Through Paracrine Platelet-derived Growth Factor-CC Signaling

Overview

Journal Nat Med

Specialties General Medicine
Molecular Biology

Date 2018 Mar 13

PMID 29529015

Citations 89

Authors

Pernilla Roswall

Matteo Bocci

Michael Bartoschek

Hong Li

Glen Kristiansen

Sara Jansson

Sophie Lehn

Jonas Sjolund

Steven Reid

Christer Larsson

Pontus Eriksson

Charlotte Anderberg

Eliane Cortez

Lao H Saal

Christina Orsmark-Pietras

Eugenia Cordero

Bengt Kristian Haller

Jari Hakkinen

Ingrid J G Burvenich

Elgene Lim

Akira Orimo

Mattias Hoglund

Lisa Ryden

Holger Moch

Andrew M Scott

Ulf Eriksson

Kristian Pietras

Affiliations

Soon will be listed here.

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.

Citing Articles

Multi-omics characterization and machine learning of lung adenocarcinoma molecular subtypes to guide precise chemotherapy and immunotherapy.

Zhang Y, Wang Y, Qian H Front Immunol. 2024; 15:1497300.

PMID: 39669580 PMC: 11634853. DOI: 10.3389/fimmu.2024.1497300.

Reversal of endocrine resistance via N6AMT1-NEDD4L pathway-mediated p110α degradation.

Ji L, Chen J, He L, Zhang F, Deng Z, Lin J Oncogene. 2024; 44(8):530-544.

PMID: 39623076 PMC: 11832415. DOI: 10.1038/s41388-024-03238-3.

KANK1 promotes breast cancer development by compromising Scribble-mediated Hippo activation.

Guo S, Liu Z, Wang G, Sun Z, Yu K, Fawcett J Nat Commun. 2024; 15(1):10381.

PMID: 39613731 PMC: 11607453. DOI: 10.1038/s41467-024-54645-9.

Characterization of the tumor microenvironment in breast cancer brain metastasis.

Li J, Lin N, Zhang S, Weng L, Chen C, Ou W Heliyon. 2024; 10(15):e34876.

PMID: 39157383 PMC: 11328047. DOI: 10.1016/j.heliyon.2024.e34876.

Functional and clinical roles of stromal PDGF receptors in tumor biology.

Strell C, Rodriguez-Tomas E, Ostman A Cancer Metastasis Rev. 2024; 43(4):1593-1609.

PMID: 38980580 PMC: 11554757. DOI: 10.1007/s10555-024-10194-7.

References

Graveel C, DeGroot J, Su Y, Koeman J, Dykema K, Leung S . Met induces diverse mammary carcinomas in mice and is associated with human basal breast cancer. Proc Natl Acad Sci U S A. 2009; 106(31):12909-14. PMC: 2722304. DOI: 10.1073/pnas.0810403106. View

Ho-Yen C, Green A, Rakha E, Brentnall A, Ellis I, Kermorgant S . C-Met in invasive breast cancer: is there a relationship with the basal-like subtype?. Cancer. 2013; 120(2):163-71. DOI: 10.1002/cncr.28386. View

Bray N, Pimentel H, Melsted P, Pachter L . Near-optimal probabilistic RNA-seq quantification. Nat Biotechnol. 2016; 34(5):525-7. DOI: 10.1038/nbt.3519. View

Subramanian A, Tamayo P, Mootha V, Mukherjee S, Ebert B, Gillette M . Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005; 102(43):15545-50. PMC: 1239896. DOI: 10.1073/pnas.0506580102. View

Brechbuhl H, Finlay-Schultz J, Yamamoto T, Gillen A, Cittelly D, Tan A . Fibroblast Subtypes Regulate Responsiveness of Luminal Breast Cancer to Estrogen. Clin Cancer Res. 2016; 23(7):1710-1721. PMC: 5378660. DOI: 10.1158/1078-0432.CCR-15-2851. View

Tam W, Lu H, Buikhuisen J, Soh B, Lim E, Reinhardt F . Protein kinase C α is a central signaling node and therapeutic target for breast cancer stem cells. Cancer Cell. 2013; 24(3):347-64. PMC: 4001722. DOI: 10.1016/j.ccr.2013.08.005. View

Kong S, Li G, Loh S, Sung W, Liu E . Cellular reprogramming by the conjoint action of ERα, FOXA1, and GATA3 to a ligand-inducible growth state. Mol Syst Biol. 2011; 7:526. PMC: 3202798. DOI: 10.1038/msb.2011.59. View

Falck A, Bendahl P, Chebil G, Olsson H, Ferno M, Ryden L . Biomarker expression and St Gallen molecular subtype classification in primary tumours, synchronous lymph node metastases and asynchronous relapses in primary breast cancer patients with 10 years' follow-up. Breast Cancer Res Treat. 2013; 140(1):93-104. DOI: 10.1007/s10549-013-2617-8. View

Kim Y, Choi J, Seo J, Song J, Lee S, Kwon M . MET is a potential target for use in combination therapy with EGFR inhibition in triple-negative/basal-like breast cancer. Int J Cancer. 2014; 134(10):2424-36. DOI: 10.1002/ijc.28566. View

10.

Horikawa S, Ishii Y, Hamashima T, Yamamoto S, Mori H, Fujimori T . PDGFRα plays a crucial role in connective tissue remodeling. Sci Rep. 2015; 5:17948. PMC: 4671150. DOI: 10.1038/srep17948. View

11.

Mei S, Qin Q, Wu Q, Sun H, Zheng R, Zang C . Cistrome Data Browser: a data portal for ChIP-Seq and chromatin accessibility data in human and mouse. Nucleic Acids Res. 2016; 45(D1):D658-D662. PMC: 5210658. DOI: 10.1093/nar/gkw983. View

12.

Parker J, Mullins M, Cheang M, Leung S, Voduc D, Vickery T . Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol. 2009; 27(8):1160-7. PMC: 2667820. DOI: 10.1200/JCO.2008.18.1370. View

13.

Marzec K, Baxter R, Martin J . Targeting Insulin-Like Growth Factor Binding Protein-3 Signaling in Triple-Negative Breast Cancer. Biomed Res Int. 2015; 2015:638526. PMC: 4499383. DOI: 10.1155/2015/638526. View

14.

Goldhirsch A, Ingle J, Gelber R, Coates A, Thurlimann B, Senn H . Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer 2009. Ann Oncol. 2009; 20(8):1319-29. PMC: 2720818. DOI: 10.1093/annonc/mdp322. View

15.

Ignatiadis M, Sotiriou C . Luminal breast cancer: from biology to treatment. Nat Rev Clin Oncol. 2013; 10(9):494-506. DOI: 10.1038/nrclinonc.2013.124. View

16.

Perou C, Sorlie T, Eisen M, van de Rijn M, Jeffrey S, Rees C . Molecular portraits of human breast tumours. Nature. 2000; 406(6797):747-52. DOI: 10.1038/35021093. View

17.

Rhim A, Oberstein P, Thomas D, Mirek E, Palermo C, Sastra S . Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma. Cancer Cell. 2014; 25(6):735-47. PMC: 4096698. DOI: 10.1016/j.ccr.2014.04.021. View

18.

Kalluri R, Zeisberg M . Fibroblasts in cancer. Nat Rev Cancer. 2006; 6(5):392-401. DOI: 10.1038/nrc1877. View

19.

Chebil G, Bendahl P, Idvall I, Ferno M . Comparison of immunohistochemical and biochemical assay of steroid receptors in primary breast cancer--clinical associations and reasons for discrepancies. Acta Oncol. 2003; 42(7):719-25. DOI: 10.1080/02841860310004724. View

20.

Badve S, Turbin D, Thorat M, Morimiya A, Nielsen T, Perou C . FOXA1 expression in breast cancer--correlation with luminal subtype A and survival. Clin Cancer Res. 2007; 13(15 Pt 1):4415-21. DOI: 10.1158/1078-0432.CCR-07-0122. View