Detecting soluble Clusterin in in-vitro and in-vivo models of prostate cancer

Abstract

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.

Identification of extracellular matrix protein 1 as a potential plasma biomarker of ESCC by proteomic analysis using iTRAQ and 2D‐LC‐MS/MS

“…CLU aberrant expression has been documented with tumor genesis of various neoplasms. In fact, overexpression of sCLU was found in many cancer types including prostate cancer , breast carcinoma , lung , bladder , and colon cancers . To date, not many reports showed a decrease in sCLU in cancers.…”

Glyceryl trinitrate‑induced cytotoxicity of docetaxel‑resistant prostatic cancer cells is associated with differential regulation of clusterin

“…The human mCRPC cell line DU145 was obtained from the American Type Culture Collection (Manassas, VA, USA). The PC3 AG and docetaxel-resistant derivative PC3-D12 cell lines were kindly provided by Professor B. Watson (University College Dublin, Dublin, Ireland) (40). The docetaxel-resistant DU145 (DU145-DR) cell line was established within the team.…”

Emerging targets to monitor and overcome docetaxel resistance in castration resistant prostate cancer (Review)

“…Only changes of concentration of the fully processed sCLU identified in the medium of CRPC cells is associated with the degree of cell line resistance to docetaxel (101). sCLU shows the characteristics of biomarker of docetaxel resistance in CRPC.…”

“…It is easily measured in the blood of patients and can be used to monitor the docetaxel effect. Biochemical recurrence-free survival in patients with elevated clusterin density was significantly shorter than in patients with normal density (101,102). CLU is also a protein of resistance to cytotoxic cytokines TRAIL, TNF-α, in CRPC cells (103,104) and a resistance protein to a variety of drugs in different tumor types: such as taxol in human mammary cancer cells (105) or in human ovarian cancer cells (106) or gemcitabine in pancreatic cancer cells (107).…”