A functional thrombin receptor (PAR1) is expressed on bone-derived prostate cancer cell lines

Christopher H. Chay, Carlton R. Cooper, James D. Gendernalik, Saravana M. Dhanasekaran, Arul M. Chinnaiyan, Mark A. Rubin, Alvin H. Schmaier, Kenneth J. Pienta

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

Abstract

Objectives. To identify genes important in prostate cancer metastatic to bone. Bone-specific metastasis is a common feature of prostate cancer and a significant cause of morbidity. Methods. To identify factors involved in organ-specific metastasis, we used cDNA microarray analysis to compare a bone-derived cell line, VCaP, with a soft tissue-derived cell line, DuCaP. Both cell lines were derived from the same patient and spontaneously passaged. Results. Forty-five genes were differentially expressed, and only seven of these also had increased expression in VCaP compared with normal prostatic tissue. Of these, protease-activated receptor 1 (PAR1) was verified as having increased expression by reverse transcriptase-polymerase chain reaction and Northern blot analysis, as well as by immunohistochemistry. PAR1 expression in a panel of prostate cancer cell lines demonstrated increased expression in those cell lines derived from bone metastases. Alpha-thrombin stimulation of the VCaP cells produced a dose-dependent mobilization of intracellular calcium compared with DuCaP, suggesting that PAR1 expressed on the VCaP prostate cancer cell line is functional. Conclusions. These data indicate that a functional PAR1 is expressed on prostate cancer cell lines. The prostate cancer cell lines expressing PAR1 appear to have an association with increased bone metastases.

Original languageEnglish (US)
Pages (from-to)760-765
Number of pages6
JournalUrology
Volume60
Issue number5
DOIs
StatePublished - Nov 1 2002
Externally publishedYes

ASJC Scopus subject areas

  • Urology

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