Mammary adipose tissue-derived lysophospholipids promote estrogen receptor-negative mammary epithelial cell proliferation

Paul A. Volden, Maxwell N. Skor, Marianna B. Johnson, Puneet Singh, Feenalie N. Patel, Martha K. McClintock, Matthew J. Brady, Suzanne D. Conzen

Research output: Contribution to journalArticle

14 Citations (Scopus)

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 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.

Original languageEnglish (US)
Pages (from-to)367-378
Number of pages12
JournalCancer Prevention Research
Volume9
Issue number5
DOIs
StatePublished - May 2016
Externally publishedYes

Fingerprint

Lysophospholipids
Estrogen Receptors
Adipose Tissue
Breast
Epithelial Cells
Cell Proliferation
Breast Neoplasms
Lysophosphatidylcholines
Adipocytes
Adipokines
lysophosphatidic acid
Fats
Phospholipases
Pathologic Processes
Conditioned Culture Medium
G-Protein-Coupled Receptors
Cell Biology

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Mammary adipose tissue-derived lysophospholipids promote estrogen receptor-negative mammary epithelial cell proliferation. / Volden, Paul A.; Skor, Maxwell N.; Johnson, Marianna B.; Singh, Puneet; Patel, Feenalie N.; McClintock, Martha K.; Brady, Matthew J.; Conzen, Suzanne D.

In: Cancer Prevention Research, Vol. 9, No. 5, 05.2016, p. 367-378.

Research output: Contribution to journalArticle

Volden, Paul A. ; Skor, Maxwell N. ; Johnson, Marianna B. ; Singh, Puneet ; Patel, Feenalie N. ; McClintock, Martha K. ; Brady, Matthew J. ; Conzen, Suzanne D. / Mammary adipose tissue-derived lysophospholipids promote estrogen receptor-negative mammary epithelial cell proliferation. In: Cancer Prevention Research. 2016 ; Vol. 9, No. 5. pp. 367-378.
@article{fabd3628d4394541b389500e5a137e07,
title = "Mammary adipose tissue-derived lysophospholipids promote estrogen receptor-negative mammary epithelial cell proliferation",
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 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.",
author = "Volden, {Paul A.} and Skor, {Maxwell N.} and Johnson, {Marianna B.} and Puneet Singh and Patel, {Feenalie N.} and McClintock, {Martha K.} and Brady, {Matthew J.} and Conzen, {Suzanne D.}",
year = "2016",
month = "5",
doi = "10.1158/1940-6207.CAPR-15-0107",
language = "English (US)",
volume = "9",
pages = "367--378",
journal = "Cancer Prevention Research",
issn = "1940-6207",
publisher = "American Association for Cancer Research Inc.",
number = "5",

}

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.

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.

UR - http://www.scopus.com/inward/record.url?scp=84969974968&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84969974968&partnerID=8YFLogxK

U2 - 10.1158/1940-6207.CAPR-15-0107

DO - 10.1158/1940-6207.CAPR-15-0107

M3 - Article

C2 - 26862086

AN - SCOPUS:84969974968

VL - 9

SP - 367

EP - 378

JO - Cancer Prevention Research

JF - Cancer Prevention Research

SN - 1940-6207

IS - 5

ER -