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Biochemical regulation of breast cancer cell expression of S1P 2 (Edg‐5) and S1P 3 (Edg‐3) G protein‐coupled receptors for sphingosine 1‐phosphate
Author(s) -
Dolezalova Hana,
Shankar Geetha,
Huang MeiChuan,
Bikle Daniel D.,
Goetzl Edward J.
Publication year - 2002
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10394
Subject(s) - sphingosine 1 phosphate , g protein coupled receptor , sphingosine , lysophosphatidic acid , receptor , chemokinesis , downregulation and upregulation , biology , microbiology and biotechnology , chemotaxis , signal transduction , cancer research , chemistry , endocrinology , biochemistry , gene
G protein‐coupled receptors (GPCRs) for lysophosphatidic acid (LPA) and sphingosine 1‐phosphate (S1P) transduce signals to many functions of normal cells. Most human cancer cells upregulate S1P and LPA GPCRs, in patterns distinctive for each type of tumor. The findings that 1‐alpha, 25‐dihydroxy‐vitamin D 3 (VD3) and all‐trans retinoic acid (RA) differentially alter expression of the predominant S1P 3 (Edg‐3) R and S1P 2 (Edg‐5) R in human breast cancer cells (BCCs) permitted analyses of their individual activities, despite a lack of selective pharmacological probes. S1P‐evoked increases in [Ca 2+ ] i in S1P 3 R‐predominant BCCs were suppressed by concentrations of VD3 and RA which decreased expression of S1P 3 Rs, despite RA‐induced increases in S1P 2 Rs. S1P‐elicited chemokinetic migration of S1P 3 R‐predominant BCCs across a type IV collagen‐coated micropore filter also was inhibited by concentrations of VD3 and RA which decreased expression of S1P 3 Rs. The RA‐induced increase in expression of S1P 2 Rs did not prevent suppression by RA of S1P‐elicited chemokinesis, which appears to be mediated by S1P 3 Rs, but instead exposed S1P 2 R‐mediated inhibition of epidermal growth factor‐stimulated chemotaxis of BCCs. In contrast, expression of the predominant LPA 2 Rs, LPA‐evoked increase in [Ca 2+ ] i and LPA‐stimulated chemokinetic migration were suppressed concomitantly by RA but not VD3. Thus two structurally‐homologous S1P Rs of BCCs differ in coupling to [Ca 2+ ] i signaling and have opposite effects on protein growth factor‐stimulated chemotaxis. © 2002 Wiley‐Liss, Inc.