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A functional thrombin receptor (PAR1) is expressed on bone-derived prostate cancer cell lines
Christopher H Chay1, Carlton R Cooper, James D Gendernalik
1Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109-0946, USA.
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.