Lysophosphatidic acid signaling in ovarian cancer

Abstract

Lysophosphatidic acid (LPA) is a bioactive phospholipid that is involved in signal transduction between cells. Plasma and ascites levels of LPA are increased in ovarian cancer patients even in the early stages and thus LPA is considered as a potential diagnostic marker for this disease. This review presents the current knowledge regarding LPA signaling in epithelial ovarian cancer. LPA stimulates proliferation, migration and invasion of ovarian cancer cells through regulation of vascular endothelial growth factor, matrix metalloproteinases, urokinase plasminogen activator, interleukin-6, interleukin-8, CXC motif chemokine ligand 12/CXC receptor 4, COX2, cyclin D1, Hippo-Yap and growth-regulated oncogene α concentrations. In this article, all of these targets and signal pathways involved in LPA influence are described.

Lysophosphatidic acid plasma concentrations in healthy subjects: circadian rhythm and associations with demographic, anthropometric and biochemical parameters

“…It was shown, that LPA participates in development of nervous [4, 5] and circulatory [6] system, functioning of male and female reproductive system [7], bone metabolism [8], hair follicles development [9], wound healing [10] and functioning of immune system [7]. On the other hand abnormalities in LPA signaling are involved in cancer progression [11] atherosclerosis [3], neuropathic pain [12], neuropsychiatric disorders [1], autoimmune diseases [1] and renal and pulmonary fibrosis [13, 14]. …”

The mechanical microenvironment regulates ovarian cancer cell morphology, migration, and spheroid disaggregation

“…This technical difference is noteworthy, as the earlier report showed that some rigidity-dependence of some experimental endpoints (i.e. migration, aspect ratio, traction stress, and traction polarization) was either reversed or normalized by treatment with lysophosphatidic acid (LPA; 89 ), an abundant component of both serum and malignant ascites that promotes migration and contractility principally through activation of Rho-dependent signaling pathways 103,104 . Another noteworthy difference between the methodology of these two studies is the use of different ECM proteins; specifically, collagen I 89 and fibronectin (this study).…”

Lysophosphatidic acid receptor isoforms expression in prostate cancer cells is differentially regulated by the CYP17A1 inhibitor abiraterone and depends on the androgen receptor

“…LPA is a pivotal growth-stimulating factor in hormone-regulated tissues, e.g. mammary, endometrial, ovarian and prostatic tissues [10,12,16,21] . The secreted lipase autotaxin hydrolyzes lysophospholipids to LPA, which subsequently binds to its receptors LPAR1-LPAR6.…”