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Cross‐talk between LPA and interleukin‐8 in human breast cancer cells
Author(s) -
Zhang Zhihong,
Meier Kathryn E
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a428
Subject(s) - lysophosphatidic acid , mapk/erk pathway , cell growth , protein kinase b , cell culture , epidermal growth factor , cancer research , cancer cell , receptor , microbiology and biotechnology , biology , signal transduction , agonist , endocrinology , medicine , chemistry , cancer , biochemistry , genetics
Inflammatory response is of interest with respect to cancer, since inflammatory mediators can stimulate many of the same pro‐mitogenic responses induced by growth factors. Lysophosphatidic acid (LPA) is a lipid mediator that elicits a broad spectrum of effects that include proliferation and inflammation. These effects are mediated by binding of LPA to G protein‐coupled receptors. The goal of this study was to determine whether LPA participates in responses to pro‐inflammatory agonists in human breast cancer cell lines. Two breast cancer cell lines, MCF‐7 and MDA‐MB‐231, were used. Both cell lines express mRNA for LPA1, LPA2, and LPA3, G protein‐coupled receptors for LPA. Isotopic labeling studies revealed that these cells generate LPA. LPA levels in medium are increased by exogenous 18:1 LPA, by epidermal growth factor (EGF), and by the pro‐inflammatory agonist interleukin‐8 (IL‐8). LPA stimulates activations of Erk and Akt kinases, and increases proliferation, in both cell lines. LPA‐induced activations of Erk and Akt, as well as proliferation, are inhibited by LPA antagonists. LPA antagonists also decrease pro‐mitogenic responses to EGF in the two cell lines. Interestingly, LPA increases production of IL‐8 by both MCF‐7 and MDA‐MB‐231 cells. These studies suggest a role for LPA in mediating cross‐talk between growth factors and inflammatory agonists in breast cancer cells. (Supported by DAMD17‐01‐1‐0730)