A functional thrombin receptor (PAR1) is expressed on bone-derived prostate cancer cell lines.
OBJECTIVE
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.
Chay
Christopher H
CH
Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109-0946, USA.
Cooper
Carlton R
CR
Gendernalik
James D
JD
Dhanasekaran
Saravana M
SM
Chinnaiyan
Arul M
AM
Rubin
Mark A
MA
Schmaier
Alvin H
AH
Pienta
Kenneth J
KJ
D001859:Bone Neoplasms / Q000235:genetics* / Q000556:secondary*; D002118:Calcium / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006490:Hemostatics / Q000494:pharmacology; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin / Q000235:genetics* / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D006490:Hemostatics; D009363:Neoplasm Proteins; D044463:Receptor, PAR-1; D018179:Receptors, Thrombin; D013917:Thrombin; D002118:Calcium