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Cancer Prev Res (Phila). 2016 May;9(5):367-78. doi: 10.1158/1940-6207.CAPR-15-0107. Epub 2016 Feb 9.

Mammary Adipose Tissue-Derived Lysophospholipids Promote Estrogen Receptor-Negative Mammary Epithelial Cell Proliferation.

Author information

1
Department of Medicine, The University of Chicago, Chicago, Illinois.
2
Department of Medicine, The University of Chicago, Chicago, Illinois. Committee on Molecular Metabolism and Nutrition, The University of Chicago, Chicago, Illinois.
3
Department of Psychology, The University of Chicago, Chicago, Illinois. Institute for Mind and Biology, The University of Chicago, Chicago, Illinois.
4
Department of Medicine, The University of Chicago, Chicago, Illinois. Committee on Molecular Metabolism and Nutrition, The University of Chicago, Chicago, Illinois. sdconzen@uchicago.edu mbrady@medicine.bsd.uchicago.edu.
5
Department of Medicine, The University of Chicago, Chicago, Illinois. Committee on Molecular Metabolism and Nutrition, The University of Chicago, Chicago, Illinois. Institute for Mind and Biology, The University of Chicago, Chicago, Illinois. Ben May Department of Cancer Research, The University of Chicago, Chicago, Illinois. sdconzen@uchicago.edu mbrady@medicine.bsd.uchicago.edu.

Abstract

Lysophosphatidic acid (LPA), acting in an autocrine or paracrine fashion through G protein-coupled receptors, has been implicated in many physiologic and pathologic processes, including cancer. LPA is converted from lysophosphatidylcholine (LPC) by the secreted phospholipase autotaxin (ATX). Although various cell types can produce ATX, adipocyte-derived ATX is believed to be the major source of circulating ATX and also to be the major regulator of plasma LPA levels. In addition to ATX, adipocytes secrete numerous other factors (adipokines); although several adipokines have been implicated in breast cancer biology, the contribution of mammary adipose tissue-derived LPC/ATX/LPA (LPA axis) signaling to breast cancer is poorly understood. Using murine mammary fat-conditioned medium, we investigated the contribution of LPA signaling to mammary epithelial cancer cell biology and identified LPA signaling as a significant contributor to the oncogenic effects of the mammary adipose tissue secretome. To interrogate the role of mammary fat in the LPA axis during breast cancer progression, we exposed mammary adipose tissue to secreted factors from estrogen receptor-negative mammary epithelial cell lines and monitored changes in the mammary fat pad LPA axis. Our data indicate that bidirectional interactions between mammary cancer cells and mammary adipocytes alter the local LPA axis and increase ATX expression in the mammary fat pad during breast cancer progression. Thus, the LPC/ATX/LPA axis may be a useful target for prevention in patients at risk of ER-negative breast cancer. Cancer Prev Res; 9(5); 367-78.

PMID:
26862086
PMCID:
PMC4854771
DOI:
10.1158/1940-6207.CAPR-15-0107
[Indexed for MEDLINE]
Free PMC Article

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