Lysophospholipids activate ovarian and breast cancer cells

Yan Xu, X. J. Fang, G. Casey, G. B. Mills

Research output: Contribution to journalArticle

234 Citations (Scopus)

Abstract

We have investigated the effects of phospholipids on activation and proliferation of ovarian and breast cancer cells. Lyso- phosphatidic acid (LPA), lysophosphatidylserine (LPS) and sphingosylphosphorylcholine (SPC) all induce transient increases in cytosolic free Ca2+ ([Ca2+](i)) in both ovarian and breast cancer cell lines. The ability of LPA, LPS and SPC to induce increases in [Ca2+](i) in ovarian and breast cancer cells is likely to be due to an interaction with cell-surface receptors as the increases in [Ca2+](i) were: (1) due to release of calcium from intracellular stores and not from transmembrane uptake due to changes in permeability; (2) blocked by lanthanum and suramin which do not enter cells; (3) blocked by phorbol esters which interrupt increases in [Ca2+](i) induced through a number of different receptors; and (4) not detected in freshly isolated peripheral blood mononuclear cells, indicating cell type specificity. In addition, increases in [Ca2+](i), induced by LPA, LPS and SPC in ovarian and breast cancer cells completely self-desensitized and cross-desensitized each other, but did not block increases in [Ca2+](i) induced by thrombin. Lysophosphatidylglycerol (LPG), but not other lysophospholipids, inhibited LPA- but not LPS- or SPC-induced increases in [Ca(2+)](i) suggesting that LPA may interact with a different receptor(s) to LPS or SPC and that their downstream signalling pathways converge or interact. LPA, SPC and LPS also induced rapid increases in tyrosine phosphorylation of specific cellular proteins, including p125(FAK) Strikingly, LPA, but not LPS or SPC, induced activation of mitogen-activated protein (MAP) kinases. Despite an ability to activate similar intracellular signalling events, LPA, LPS and SPC exhibited markedly different effects on cell proliferation. Whereas LPA induced a significant increase in cell proliferation, LPS did not substantially alter cell proliferation and SPC inhibited cell proliferation. Surprisingly, phosphatidic acid (PA), which did not induce increases in [Ca2+](i), p125(FAK) activation or activation of MAP kinases, did induce proliferation of ovarian cancer cells, albeit at higher concentrations that LPA. The discordance between sensitivity to LPG, early biochemical events stimulated, and the eventual proliferation response combine to suggest that LPA probably utilizes a different receptor from LPS, SPC and PA. Therefore ovarian and breast cancer cells are sensitive to the effects of a number of different phospholipids which may play a role in the growth of these tumour cells in the cancer patient and are thus potential targets for therapy.

Original languageEnglish (US)
Pages (from-to)933-940
Number of pages8
JournalBiochemical Journal
Volume309
Issue number3
StatePublished - 1995
Externally publishedYes

Fingerprint

Lysophospholipids
Phosphatidic Acids
Ovarian Neoplasms
Cells
Breast Neoplasms
Cell proliferation
Chemical activation
Cell Proliferation
Mitogen-Activated Protein Kinases
Phospholipids
sphingosine phosphorylcholine
lysophosphatidylserine
Suramin
Lanthanum
Phosphorylation
Cell Surface Receptors
Phorbol Esters
Thrombin

ASJC Scopus subject areas

  • Biochemistry

Cite this

Xu, Y., Fang, X. J., Casey, G., & Mills, G. B. (1995). Lysophospholipids activate ovarian and breast cancer cells. Biochemical Journal, 309(3), 933-940.

Lysophospholipids activate ovarian and breast cancer cells. / Xu, Yan; Fang, X. J.; Casey, G.; Mills, G. B.

In: Biochemical Journal, Vol. 309, No. 3, 1995, p. 933-940.

Research output: Contribution to journalArticle

Xu, Y, Fang, XJ, Casey, G & Mills, GB 1995, 'Lysophospholipids activate ovarian and breast cancer cells', Biochemical Journal, vol. 309, no. 3, pp. 933-940.
Xu Y, Fang XJ, Casey G, Mills GB. Lysophospholipids activate ovarian and breast cancer cells. Biochemical Journal. 1995;309(3):933-940.
Xu, Yan ; Fang, X. J. ; Casey, G. ; Mills, G. B. / Lysophospholipids activate ovarian and breast cancer cells. In: Biochemical Journal. 1995 ; Vol. 309, No. 3. pp. 933-940.
@article{efc311b738914dafbd7cbbc769dadd21,
title = "Lysophospholipids activate ovarian and breast cancer cells",
abstract = "We have investigated the effects of phospholipids on activation and proliferation of ovarian and breast cancer cells. Lyso- phosphatidic acid (LPA), lysophosphatidylserine (LPS) and sphingosylphosphorylcholine (SPC) all induce transient increases in cytosolic free Ca2+ ([Ca2+](i)) in both ovarian and breast cancer cell lines. The ability of LPA, LPS and SPC to induce increases in [Ca2+](i) in ovarian and breast cancer cells is likely to be due to an interaction with cell-surface receptors as the increases in [Ca2+](i) were: (1) due to release of calcium from intracellular stores and not from transmembrane uptake due to changes in permeability; (2) blocked by lanthanum and suramin which do not enter cells; (3) blocked by phorbol esters which interrupt increases in [Ca2+](i) induced through a number of different receptors; and (4) not detected in freshly isolated peripheral blood mononuclear cells, indicating cell type specificity. In addition, increases in [Ca2+](i), induced by LPA, LPS and SPC in ovarian and breast cancer cells completely self-desensitized and cross-desensitized each other, but did not block increases in [Ca2+](i) induced by thrombin. Lysophosphatidylglycerol (LPG), but not other lysophospholipids, inhibited LPA- but not LPS- or SPC-induced increases in [Ca(2+)](i) suggesting that LPA may interact with a different receptor(s) to LPS or SPC and that their downstream signalling pathways converge or interact. LPA, SPC and LPS also induced rapid increases in tyrosine phosphorylation of specific cellular proteins, including p125(FAK) Strikingly, LPA, but not LPS or SPC, induced activation of mitogen-activated protein (MAP) kinases. Despite an ability to activate similar intracellular signalling events, LPA, LPS and SPC exhibited markedly different effects on cell proliferation. Whereas LPA induced a significant increase in cell proliferation, LPS did not substantially alter cell proliferation and SPC inhibited cell proliferation. Surprisingly, phosphatidic acid (PA), which did not induce increases in [Ca2+](i), p125(FAK) activation or activation of MAP kinases, did induce proliferation of ovarian cancer cells, albeit at higher concentrations that LPA. The discordance between sensitivity to LPG, early biochemical events stimulated, and the eventual proliferation response combine to suggest that LPA probably utilizes a different receptor from LPS, SPC and PA. Therefore ovarian and breast cancer cells are sensitive to the effects of a number of different phospholipids which may play a role in the growth of these tumour cells in the cancer patient and are thus potential targets for therapy.",
author = "Yan Xu and Fang, {X. J.} and G. Casey and Mills, {G. B.}",
year = "1995",
language = "English (US)",
volume = "309",
pages = "933--940",
journal = "Biochemical Journal",
issn = "0264-6021",
publisher = "Portland Press Ltd.",
number = "3",

}

TY - JOUR

T1 - Lysophospholipids activate ovarian and breast cancer cells

AU - Xu, Yan

AU - Fang, X. J.

AU - Casey, G.

AU - Mills, G. B.

PY - 1995

Y1 - 1995

N2 - We have investigated the effects of phospholipids on activation and proliferation of ovarian and breast cancer cells. Lyso- phosphatidic acid (LPA), lysophosphatidylserine (LPS) and sphingosylphosphorylcholine (SPC) all induce transient increases in cytosolic free Ca2+ ([Ca2+](i)) in both ovarian and breast cancer cell lines. The ability of LPA, LPS and SPC to induce increases in [Ca2+](i) in ovarian and breast cancer cells is likely to be due to an interaction with cell-surface receptors as the increases in [Ca2+](i) were: (1) due to release of calcium from intracellular stores and not from transmembrane uptake due to changes in permeability; (2) blocked by lanthanum and suramin which do not enter cells; (3) blocked by phorbol esters which interrupt increases in [Ca2+](i) induced through a number of different receptors; and (4) not detected in freshly isolated peripheral blood mononuclear cells, indicating cell type specificity. In addition, increases in [Ca2+](i), induced by LPA, LPS and SPC in ovarian and breast cancer cells completely self-desensitized and cross-desensitized each other, but did not block increases in [Ca2+](i) induced by thrombin. Lysophosphatidylglycerol (LPG), but not other lysophospholipids, inhibited LPA- but not LPS- or SPC-induced increases in [Ca(2+)](i) suggesting that LPA may interact with a different receptor(s) to LPS or SPC and that their downstream signalling pathways converge or interact. LPA, SPC and LPS also induced rapid increases in tyrosine phosphorylation of specific cellular proteins, including p125(FAK) Strikingly, LPA, but not LPS or SPC, induced activation of mitogen-activated protein (MAP) kinases. Despite an ability to activate similar intracellular signalling events, LPA, LPS and SPC exhibited markedly different effects on cell proliferation. Whereas LPA induced a significant increase in cell proliferation, LPS did not substantially alter cell proliferation and SPC inhibited cell proliferation. Surprisingly, phosphatidic acid (PA), which did not induce increases in [Ca2+](i), p125(FAK) activation or activation of MAP kinases, did induce proliferation of ovarian cancer cells, albeit at higher concentrations that LPA. The discordance between sensitivity to LPG, early biochemical events stimulated, and the eventual proliferation response combine to suggest that LPA probably utilizes a different receptor from LPS, SPC and PA. Therefore ovarian and breast cancer cells are sensitive to the effects of a number of different phospholipids which may play a role in the growth of these tumour cells in the cancer patient and are thus potential targets for therapy.

AB - We have investigated the effects of phospholipids on activation and proliferation of ovarian and breast cancer cells. Lyso- phosphatidic acid (LPA), lysophosphatidylserine (LPS) and sphingosylphosphorylcholine (SPC) all induce transient increases in cytosolic free Ca2+ ([Ca2+](i)) in both ovarian and breast cancer cell lines. The ability of LPA, LPS and SPC to induce increases in [Ca2+](i) in ovarian and breast cancer cells is likely to be due to an interaction with cell-surface receptors as the increases in [Ca2+](i) were: (1) due to release of calcium from intracellular stores and not from transmembrane uptake due to changes in permeability; (2) blocked by lanthanum and suramin which do not enter cells; (3) blocked by phorbol esters which interrupt increases in [Ca2+](i) induced through a number of different receptors; and (4) not detected in freshly isolated peripheral blood mononuclear cells, indicating cell type specificity. In addition, increases in [Ca2+](i), induced by LPA, LPS and SPC in ovarian and breast cancer cells completely self-desensitized and cross-desensitized each other, but did not block increases in [Ca2+](i) induced by thrombin. Lysophosphatidylglycerol (LPG), but not other lysophospholipids, inhibited LPA- but not LPS- or SPC-induced increases in [Ca(2+)](i) suggesting that LPA may interact with a different receptor(s) to LPS or SPC and that their downstream signalling pathways converge or interact. LPA, SPC and LPS also induced rapid increases in tyrosine phosphorylation of specific cellular proteins, including p125(FAK) Strikingly, LPA, but not LPS or SPC, induced activation of mitogen-activated protein (MAP) kinases. Despite an ability to activate similar intracellular signalling events, LPA, LPS and SPC exhibited markedly different effects on cell proliferation. Whereas LPA induced a significant increase in cell proliferation, LPS did not substantially alter cell proliferation and SPC inhibited cell proliferation. Surprisingly, phosphatidic acid (PA), which did not induce increases in [Ca2+](i), p125(FAK) activation or activation of MAP kinases, did induce proliferation of ovarian cancer cells, albeit at higher concentrations that LPA. The discordance between sensitivity to LPG, early biochemical events stimulated, and the eventual proliferation response combine to suggest that LPA probably utilizes a different receptor from LPS, SPC and PA. Therefore ovarian and breast cancer cells are sensitive to the effects of a number of different phospholipids which may play a role in the growth of these tumour cells in the cancer patient and are thus potential targets for therapy.

UR - http://www.scopus.com/inward/record.url?scp=0029126484&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029126484&partnerID=8YFLogxK

M3 - Article

C2 - 7639713

AN - SCOPUS:0029126484

VL - 309

SP - 933

EP - 940

JO - Biochemical Journal

JF - Biochemical Journal

SN - 0264-6021

IS - 3

ER -