TY - JOUR
T1 - Mammary adipose tissue-derived lysophospholipids promote estrogen receptor-negative mammary epithelial cell proliferation
AU - Volden, Paul A.
AU - Skor, Maxwell N.
AU - Johnson, Marianna B.
AU - Singh, Puneet
AU - Patel, Feenalie N.
AU - McClintock, Martha K.
AU - Brady, Matthew J.
AU - Conzen, Suzanne D.
N1 - Funding Information:
This work was supported by NIH grants R01-CA148814 to S.D. Conzen and M.K. McClintock, DOD Idea Award BC 061754 and U.S. Army W81XWH-07-1-0296 to M.K. McClintock, NIH 1 T32 DK087703 and a DOD pre-doctoral fellowship W81XWH-11-1-014901 to P. A. Volden, and by the University of Chicago Comprehensive Cancer Center (NIH P30 CA14599) supported cores: Pathology, Microscopic Imaging and NMR Cores. The lipidomics analyses were performed at the KLRC Analytical Laboratory. Instrument acquisition and lipidomics method development was supported by National Science Foundation (EPS 0236913, MCB 0920663, DBI 0521587, and DBI1228622), Kansas Technology Enterprise Corporation, K-IDeA Networks of Biomedical Research Excellence (INBRE) of National Institute of Health (P20GM103418), and Kansas State University. Targeted LPA and LPC analyses were performed by the Wayne State Lipidomics Core Facility that is supported in part by the NIH National Center for Research Resources (S10 RR027926).
Publisher Copyright:
©2016 AACR.
PY - 2016/5
Y1 - 2016/5
N2 - 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 themammaryfat 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.
AB - 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 themammaryfat 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.
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U2 - 10.1158/1940-6207.CAPR-15-0107
DO - 10.1158/1940-6207.CAPR-15-0107
M3 - Article
C2 - 26862086
AN - SCOPUS:84969974968
SN - 1940-6207
VL - 9
SP - 367
EP - 378
JO - Cancer Prevention Research
JF - Cancer Prevention Research
IS - 5
ER -