Lysophosphatidic acid is a major regulator of growth-regulated oncogene alpha in ovarian cancer

Cancer Research
Zendra P LeeXianjun Fang

Abstract

Growth-regulated oncogene alpha (GROalpha), a member of the chemokine superfamily, is commonly expressed in transformed cells and contributes to angiogenesis and tumorigenesis. Here, we report that increased GROalpha levels are detected in the plasma and ascites of ovarian cancer patients. Ovarian cancer cell lines in culture express and secrete GROalpha. However, when they are starved in serum-free medium, ovarian cancer cells ceased producing GROalpha, suggesting that GROalpha is not constitutively expressed but rather is produced in response to exogenous growth factors in ovarian cancer cells. The prototype peptide growth factors present in serum such as platelet-derived growth factor, insulin-like growth factor I, and insulin do not stimulate GROalpha production by ovarian cancer cells. In contrast, lysophosphatidic acid (LPA), a glycerol backbone phospholipid mediator present in serum and ascites of ovarian cancer patients, is a potent inducer of GROalpha expression in ovarian cancer cell lines. Treatment of ovarian cancer cells with LPA leads to transcriptional activation of the GROalpha gene promoter and robust accumulation of GROalpha protein in culture supernatants. The action of LPA on GROalpha expression is mediated ...Continue Reading

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