TY - JOUR
T1 - A functional thrombin receptor (PAR1) is expressed on bone-derived prostate cancer cell lines
AU - Chay, Christopher H.
AU - Cooper, Carlton R.
AU - Gendernalik, James D.
AU - Dhanasekaran, Saravana M.
AU - Chinnaiyan, Arul M.
AU - Rubin, Mark A.
AU - Schmaier, Alvin H.
AU - Pienta, Kenneth J.
N1 - Funding Information:
This work was supported by the SPORE grant at the University of Michigan Comprehensive Cancer Center (P50 CA 69568), Comprehensive Cancer grant CA 46592, HL52779, HL61981, and a grant from the Michigan Life Science Corridor (grant 1607). C. H. Chay is supported by a 2001 American Foundation for Urological Disease Fellowship (Amgen & PRAECIS).
PY - 2002/11/1
Y1 - 2002/11/1
N2 - 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.
AB - 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.
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U2 - 10.1016/S0090-4295(02)01969-6
DO - 10.1016/S0090-4295(02)01969-6
M3 - Article
C2 - 12429291
AN - SCOPUS:0036845746
SN - 0090-4295
VL - 60
SP - 760
EP - 765
JO - Urology
JF - Urology
IS - 5
ER -