Lysophospholipid mediators of immunity and neoplasia.
Lysophosphatidic acid (LPA), sphingosine 1-phosphate (S1P) and some other structurally related lysophospholipids are active growth factors and stimuli for diverse cellular functions. LPA and S1P promote early T cell migration to tissue sites of immune responses and regulate T cell proliferation and secretion of numerous cytokines. Edg-4 (LPA2) LPA receptors, which are constitutively expressed by helper T cells, and Edg-2 (LPA1) LPA receptors, which are expressed only by activated helper T cells, transduce opposite effects of LPA on some T cell responses. A similar mechanism is observed for fine regulation of Edg R-mediated effects of LPA on ovarian cancer cells. Edg-4 (LPA2) R transduces proliferative responses, recruitment of autocrine protein growth factors, and migration of ovarian cancer cells, whereas Edg-2 (LPA1) R transduces inhibition of Edg-4 (LPA2) R-mediated responses and concurrently elicits apoptosis and anoikis of ovarian cancer cells. Edg-4 (LPA2) R is a distinctive functional marker for ovarian carcinoma, and is expressed both as the wild-type and a carboxyl-terminally extended gain-of-function mutant. Newly discovered non-lipid agonists and antagonists for individual Edg receptors will permit more sophisticated analyses of their respective contributions in human biology and pathophysiology, and may represent novel therapeutic modalities in immune disorders and cancer.
Huang
Mei Chuan
MC
UB8B, UC Box 0711, Department of Medicine, University of California Medical Center, 533 Parnassus at 4th Avenue, San Francisco, CA 94143-0711, USA.
Graeler
Markus
M
Shankar
Geetha
G
Spencer
Juliet
J
Goetzl
Edward J
EJ
D000818:Animals; D006133:Growth Substances / Q000276:immunology / Q000502:physiology; D006801:Humans; D007107:Immune System / Q000502:physiology*; D008246:Lysophospholipids / Q000276:immunology / Q000502:physiology*; D009369:Neoplasms / Q000503:physiopathology*
D006133:Growth Substances; D008246:Lysophospholipids