Biochemical regulation of breast cancer cell expression of S1P2 (Edg-5) and S1P3 (Edg-3) G protein-coupled receptors for sphingosine 1-phosphate

✍ Scribed by Hana Dolezalova; Geetha Shankar; Mei-Chuan Huang; Daniel D. Bikle; Edward J. Goetzl

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 310 KB
• Volume: 88
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.10394

✦ Synopsis

Abstract

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.