Skip to main content

Role of decreased levels of lipid phosphate phosphatase-1 in accumulation of lysophosphatidic acid in ovarian cancer.

Publication ,  Journal Article
Tanyi, JL; Hasegawa, Y; Lapushin, R; Morris, AJ; Wolf, JK; Berchuck, A; Lu, K; Smith, DI; Kalli, K; Hartmann, LC; McCune, K; Fishman, D ...
Published in: Clin Cancer Res
September 1, 2003

The levels of lysophosphatidic acid (LPA) are consistently elevated in the ascites of ovarian cancer patients, suggesting that ovarian cancer cells are exposed to an LPA replete environment. LPA stimulates cell proliferation, cell survival, resistance to cisplatin, production and activation of proteases, invasiveness and production of the neovascularizing factors, vascular endothelial growth factor, and interleukin 8. Although ovarian cancer cells can produce LPA, this may not be the major reason for altered LPA levels in ascites. We have demonstrated that the major mechanism of degradation of LPA by ovarian cancer cells is through a lipid phosphate phosphatase (LPP)-like activity. We demonstrate herein that LPP-1 mRNA is decreased in the majority of ovarian cancers. This is recapitulated in ovarian cancer cell lines, where LPP-1 RNA levels are lower than those in normal ovarian epithelium and immortalized ovarian epithelial cells. Introduction of LPP-1 into ovarian cancer cell lines results in increased LPA hydrolysis, which is associated with a marked inhibition of cell proliferation and colony-forming activity and a marked increase in apoptosis. Thus, the LPA-rich environment of the ovarian cancer cell in vivo and the subsequent effects of cellular pathophysiology may be a consequence of both increased LPA production and decreased LPA metabolism by ovarian cancer cells.

Duke Scholars

Published In

Clin Cancer Res

ISSN

1078-0432

Publication Date

September 1, 2003

Volume

9

Issue

10 Pt 1

Start / End Page

3534 / 3545

Location

United States

Related Subject Headings

  • Transfection
  • Telomerase
  • Reverse Transcriptase Polymerase Chain Reaction
  • RNA, Messenger
  • RNA
  • Promoter Regions, Genetic
  • Precipitin Tests
  • Phosphatidate Phosphatase
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Tanyi, J. L., Hasegawa, Y., Lapushin, R., Morris, A. J., Wolf, J. K., Berchuck, A., … Mills, G. B. (2003). Role of decreased levels of lipid phosphate phosphatase-1 in accumulation of lysophosphatidic acid in ovarian cancer. Clin Cancer Res, 9(10 Pt 1), 3534–3545.
Tanyi, Janos L., Yutaka Hasegawa, Ruth Lapushin, Andrew J. Morris, Judith K. Wolf, Andrew Berchuck, Karen Lu, et al. “Role of decreased levels of lipid phosphate phosphatase-1 in accumulation of lysophosphatidic acid in ovarian cancer.Clin Cancer Res 9, no. 10 Pt 1 (September 1, 2003): 3534–45.
Tanyi JL, Hasegawa Y, Lapushin R, Morris AJ, Wolf JK, Berchuck A, et al. Role of decreased levels of lipid phosphate phosphatase-1 in accumulation of lysophosphatidic acid in ovarian cancer. Clin Cancer Res. 2003 Sep 1;9(10 Pt 1):3534–45.
Tanyi, Janos L., et al. “Role of decreased levels of lipid phosphate phosphatase-1 in accumulation of lysophosphatidic acid in ovarian cancer.Clin Cancer Res, vol. 9, no. 10 Pt 1, Sept. 2003, pp. 3534–45.
Tanyi JL, Hasegawa Y, Lapushin R, Morris AJ, Wolf JK, Berchuck A, Lu K, Smith DI, Kalli K, Hartmann LC, McCune K, Fishman D, Broaddus R, Cheng KW, Atkinson EN, Yamal JM, Bast RC, Felix EA, Newman RA, Mills GB. Role of decreased levels of lipid phosphate phosphatase-1 in accumulation of lysophosphatidic acid in ovarian cancer. Clin Cancer Res. 2003 Sep 1;9(10 Pt 1):3534–3545.

Published In

Clin Cancer Res

ISSN

1078-0432

Publication Date

September 1, 2003

Volume

9

Issue

10 Pt 1

Start / End Page

3534 / 3545

Location

United States

Related Subject Headings

  • Transfection
  • Telomerase
  • Reverse Transcriptase Polymerase Chain Reaction
  • RNA, Messenger
  • RNA
  • Promoter Regions, Genetic
  • Precipitin Tests
  • Phosphatidate Phosphatase
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis