Role for 18:1 lysophosphatidic acid as an autocrine mediator in prostate cancer cells

Yuhuan Xie; Terra C Gibbs; Yurii V Mukhin; Kathryn E Meier

doi:10.1074/jbc.M203864200

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Role for 18:1 lysophosphatidic acid as an autocrine mediator in prostate cancer cells

Journal article

Open access

Peer reviewed

Role for 18:1 lysophosphatidic acid as an autocrine mediator in prostate cancer cells

Yuhuan Xie, Terra C Gibbs, Yurii V Mukhin and Kathryn E Meier

The Journal of biological chemistry, Vol.277(36), pp.32516-32526

09/06/2002

DOI: https://doi.org/10.1074/jbc.M203864200

Handle:

https://hdl.handle.net/2376/110397

PMID: 12084719

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Abstract

Autocrine Communication

Lysophospholipids - metabolism

Prostatic Neoplasms - metabolism

Phosphorylation

Signal Transduction

Calcium - metabolism

Protein-Tyrosine Kinases - metabolism

Humans

Focal Adhesion Protein-Tyrosine Kinases

Immunoblotting

Male

Focal Adhesion Kinase 1

Phospholipase D - metabolism

Dose-Response Relationship, Drug

Spectrometry, Mass, Electrospray Ionization

Bombesin - pharmacology

Time Factors

Mass Spectrometry

Tumor Cells, Cultured

Lysophospholipids - physiology

Mitogen-Activated Protein Kinases - metabolism

Lysophosphatidic acid (LPA) is a lipid mediator that may play an important role in growth and survival of carcinomas. In this study, LPA production and response were characterized in two human prostate cancer (CaP) cell lines: PC-3 and Du145. Bombesin, a neuroendocrine peptide that is mitogenic for CaP cells, stimulated focal adhesion kinase phosphorylation and activated the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway. Similar responses were elicited by 18:1 LPA (oleoyl-LPA). Studies using radioisotopic labeling revealed that both PC-3 and Du145 generate LPA and that LPA production is increased by bombesin. The kinetics of bombesin-induced phospholipase D activation and LPA production were similar. Using electrospray ionization mass spectrometry, 18:1 LPA was found to be an abundant LPA species in CaP cell medium. Structure activity studies of acyl-LPAs revealed that 18:1 LPA is most efficacious for activation of extracellular signal-regulated kinase and phospholipase D in CaP cells. Incubation with 18:1 LPA caused homologous desensitization of LPA response, whereas bombesin caused heterologous desensitization. LPA was present at nanomolar levels in medium from bombesin-treated cells. LPA extracted from the medium induced calcium mobilization in CaP cells. These results demonstrate that bioactive LPA is generated by CaP cells in response to a mitogen and suggest that 18:1 LPA can act as an autocrine mediator.

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Title: Role for 18:1 lysophosphatidic acid as an autocrine mediator in prostate cancer cells
Creators: Yuhuan Xie - Department of Pharmacology and Medicine and the Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina 29425, USA
Terra C Gibbs
Yurii V Mukhin
Kathryn E Meier
Publication Details: The Journal of biological chemistry, Vol.277(36), pp.32516-32526
Academic Unit: Pharmaceutical Sciences, Department of
Publisher: United States
Grant note: S10-RR013005 / NCRR NIH HHS
Identifiers: 99900547544701842
Language: English
Resource Type: Journal article