Overexpression of Edg-2/vzg-1 induces apoptosis and anoikis in ovarian cancer cells in a lysophosphatidic acid-independent manner

Tatsuro Furui, Ruth LaPushin, Muling Mao, Humera Khan, Steve R. Watt, Mary Ann V. Watt, Yiling Lu, Xianjun Fang, Shinichi Tsutsui, Zahid H. Siddik, Robert C. Bast, Gordon Mills

Research output: Contribution to journalArticle

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Abstract

Lysophosphatidic acid (LPA) is one of the major growth factors in ascites from ovarian cancer patients and appears to play an important role in proliferation, survival, and invasion of ovarian cancer cells. Recently, several groups have shown that Edg-2, which belongs to the G-protein coupled receptor family, is a functional LPA receptor. Northern blot analysis showed that most ovarian cancer cell lines express Edg-2. Edg-2 expression was especially high in the cisplatin-resistant and slowly proliferating 2780cp cell line and was almost absent from the cisplatin-sensitive and rapidly proliferating A2780 cell line. We thus assessed whether Edg-2 could contribute to changes in cell viability, cell proliferation, or cisplatin resistance. Stable overexpression of Edg-2 in A2780 cells induced an exogenous LPA-independent decrease in proliferation but did not alter cisplatin sensitivity. The LPA-independent decrease in growth rate induced by overexpression of Edg-2 could be explained, at least in part, by Edg-2- induced apoptosis rather than by effects on cell cycle progression. In agreement with the results in stably transfected A2780 cells, transient expression of Edg-2 in Jurkat T cells also induced apoptosis. When cells were separated from the extracellular matrix, they underwent a specialized form of apoptosis called anoikis, which is particularly important in survival of cells in the circulation during metastasis. A2780 cells engineered to overexpress Edg-2 were particularly sensitive to anoikis. These observations suggest that Edg-2 may be a negative regulator for ovarian epithelial cell growth and metastasis.

Original languageEnglish (US)
Pages (from-to)4308-4318
Number of pages11
JournalClinical Cancer Research
Volume5
Issue number12
StatePublished - Dec 1 1999
Externally publishedYes

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Anoikis
Ovarian Neoplasms
Cisplatin
Apoptosis
Cell Line
Cell Survival
Lysophosphatidic Acid Receptors
Neoplasm Metastasis
Jurkat Cells
Growth
G-Protein-Coupled Receptors
Ascites
Northern Blotting
Extracellular Matrix
Intercellular Signaling Peptides and Proteins
Cell Cycle
Epithelial Cells
Cell Proliferation
lysophosphatidic acid
T-Lymphocytes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Overexpression of Edg-2/vzg-1 induces apoptosis and anoikis in ovarian cancer cells in a lysophosphatidic acid-independent manner. / Furui, Tatsuro; LaPushin, Ruth; Mao, Muling; Khan, Humera; Watt, Steve R.; Watt, Mary Ann V.; Lu, Yiling; Fang, Xianjun; Tsutsui, Shinichi; Siddik, Zahid H.; Bast, Robert C.; Mills, Gordon.

In: Clinical Cancer Research, Vol. 5, No. 12, 01.12.1999, p. 4308-4318.

Research output: Contribution to journalArticle

Furui, T, LaPushin, R, Mao, M, Khan, H, Watt, SR, Watt, MAV, Lu, Y, Fang, X, Tsutsui, S, Siddik, ZH, Bast, RC & Mills, G 1999, 'Overexpression of Edg-2/vzg-1 induces apoptosis and anoikis in ovarian cancer cells in a lysophosphatidic acid-independent manner', Clinical Cancer Research, vol. 5, no. 12, pp. 4308-4318.
Furui, Tatsuro ; LaPushin, Ruth ; Mao, Muling ; Khan, Humera ; Watt, Steve R. ; Watt, Mary Ann V. ; Lu, Yiling ; Fang, Xianjun ; Tsutsui, Shinichi ; Siddik, Zahid H. ; Bast, Robert C. ; Mills, Gordon. / Overexpression of Edg-2/vzg-1 induces apoptosis and anoikis in ovarian cancer cells in a lysophosphatidic acid-independent manner. In: Clinical Cancer Research. 1999 ; Vol. 5, No. 12. pp. 4308-4318.
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AU - Khan, Humera

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AU - Watt, Mary Ann V.

AU - Lu, Yiling

AU - Fang, Xianjun

AU - Tsutsui, Shinichi

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AU - Bast, Robert C.

AU - Mills, Gordon

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