Detecting soluble clusterin in in-vitro and in-vivo models of prostate cancer.
PSA, the only relevant marker for prostate cancer, has a low predictive value; moreover its low threshold leads to unnecessary biopsies with associated complications. Identification of prognostic factors is an important goal in prostate cancer. In the search for new markers, clusterin, has some potential as it is closely linked with cancer progression and resistance to apoptosis. We looked at the expression of secreted clusterin (sCLU) in prostate cells to determine correlations with progression and drug resistance. The plasmatic expression of sCLU was also investigated in order to use it as a potential marker for prostate cancer. sCLU expression was studied using Western blotting on cultured prostate cells, PWR-1E, PC3 and PC3 Docetaxel resistant cells in the cytosol and culture medium. An inhouse ELISA test was developed to determine sCLU expression in culture media and plasma samples. A patient cohort was identified from the Prostate Cancer Research Consortium Bio-Resource and plasmatic expression of sCLU was studied using western blotting and the inhouse ELISA test. Only the fully processed form of sCLU was identified in the medium of cells with increased expression associated with increased progression of disease and resistance to docetaxel. Plasmatic expression of sCLU was significantly higher in the plasma of patients with high grade prostate cancer with extracapsular extension than in the plasma of prostate cancer patients without extracapsular extension. Plasmatic sCLU may be an effective prognostic marker of prostate cancer and needs to be tested in a multimarker approach.
Girard
F P
FP
UCD School of Medicine and Medical Science, University College Dublin, Ireland. frederic.girard@sls.aphp
Byrne
J
J
Downes
M
M
Fanning
D
D
Desgrandchamps
F
F
Fitzpatrick
J M
JM
Watson
R W
RW
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D045744:Cell Line, Tumor; D051152:Clusterin / Q000032:analysis* / Q000097:blood / Q000652:urine; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000737:chemistry*
D014408:Biomarkers, Tumor; C495242:CLU protein, human; D051152:Clusterin