Prosaposin, a novel tumor marker for prostate cancer

Summary

Principal Investigator: Shahriar Koochekpour
Abstract: [unreadable] DESCRIPTION (provided by applicant): Identification of tumor markers that are expressed at high amounts only in malignant state and correlate with disease stage and progression are needed to improve the diagnosis and treatment of prostate cancer (PCa). We have cloned prosaposin from the poorly differentiated androgen-independent (Al) PCa cell line, PC-3. Our results to date show: 1) prosaposin expression is higher in metastatic Al than in androgen-dependent (AD) PCa cells, 2) serum levels of prosaposin is higher in hormone-refractory PCa patients than in the normal male population, 3) prosaposin gene is amplified in PCa cells and punch biopsy specimens of prostate cancer xenografts and metastatic lymph nodes, and 4) prosaposin stimulates growth, migration, and invasion and acts as a cell survival and anti-apoptotic factor in both AD and Al PCa cells. These results lead us to propose the hypothesis that prosaposin contributes to prostate carcinogenesis and has the characteristics of a PCa tumor marker. Thus, the goal of this project is to establish the usefulness of this molecule as a tumor marker for prostate cancer. The Specific Aims of this R21 project are: 1. To assess, in proliferating tumor cells from prostate cancer tissues, the relationship between prosaposin expression and patients' Gleason's score and serum-PSA level. We will use immunohistochemical staining and tissue microarray to measure prosaposin expression level in proliferating (Ki-67 positive) tumor cells and its relationship with the two most important current predictive factors, Gleason's score (GS) and PSA. 2. To define the clinical significance of prosaposin expression as a marker of differentiation or disease progression in prostate cancer. Using sensitive quantitative laser capture microdissection, Real-Time PCR, and DELFIA-prosaposin immunoquantification assays, we will: a) in frozen tissue sections of radical prostatectomy specimens, assess the correlation between prosaposin (mRNA and protein) expression and dominant Gleason's pattern (as a measure of glandular differentiation), and b) in sera from patients, evaluate the relationship between prosaposin and metastatic versus non-metastatic PCa, hormone-sensitive versus hormone-refractory, and other prognostic or risk factors (e.g., PSA, GS, age, race) Significance. The results of this exploratory (R21) project will provide the basis for design of future large- scale prospective clinical investigation that will test the validity, reliability, and predictability of prosaposin as a tumor marker in relationship to PCa severity, progression, response to treatment, and outcomes. [unreadable] [unreadable] [unreadable]
Funding Period: 2006-04-01 - 2008-03-31
more information: NIH RePORT

Top Publications

  1. pmc Identification of a novel germline missense mutation of the androgen receptor in African American men with familial prostate cancer
    Si Yi Hu
    Stanley S Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
    Asian J Androl 12:336-43. 2010
  2. pmc Serum prosaposin levels are increased in patients with advanced prostate cancer
    Shahriar Koochekpour
    Department of Urology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA
    Prostate 72:253-69. 2012
  3. ncbi Prosaposin upregulates AR and PSA expression and activity in prostate cancer cells (LNCaP)
    Shahriar Koochekpour
    Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA
    Prostate 67:178-89. 2007
  4. ncbi Prosaposin is a novel androgen-regulated gene in prostate cancer cell line LNCaP
    S Koochekpour
    Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA
    J Cell Biochem 101:631-41. 2007
  5. ncbi Prosaposin is an AR-target gene and its neurotrophic domain upregulates AR expression and activity in prostate stromal cells
    S Koochekpour
    Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA
    J Cell Biochem 104:2272-85. 2008
  6. pmc Prosaposin down-modulation decreases metastatic prostate cancer cell adhesion, migration, and invasion
    Siyi Hu
    Stanley S Scott Cancer Center, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
    Mol Cancer 9:30. 2010

Scientific Experts

Detail Information

Publications6

  1. pmc Identification of a novel germline missense mutation of the androgen receptor in African American men with familial prostate cancer
    Si Yi Hu
    Stanley S Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
    Asian J Androl 12:336-43. 2010
    ..Additional studies will be required to define the frequency and contribution of the AR (A1675T) allele to early-onset and/or familial PCa in African Americans...
  2. pmc Serum prosaposin levels are increased in patients with advanced prostate cancer
    Shahriar Koochekpour
    Department of Urology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA
    Prostate 72:253-69. 2012
    ..The clinicohistopathological significance of serum PSAP levels and its tissue expression and association with predictive or prognostic variable in primary or advanced PCa are not known...
  3. ncbi Prosaposin upregulates AR and PSA expression and activity in prostate cancer cells (LNCaP)
    Shahriar Koochekpour
    Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA
    Prostate 67:178-89. 2007
    ..Here, we explored the possibility for a functional relationship between prosaposin and androgen receptor (AR) in LNCaP cells...
  4. ncbi Prosaposin is a novel androgen-regulated gene in prostate cancer cell line LNCaP
    S Koochekpour
    Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA
    J Cell Biochem 101:631-41. 2007
    ..This observation, together with the pleiotropic growth factor activity of prosaposin, might suggest a role for this molecule in AR-dependent progression of prostate cancer at its early or late AI-state...
  5. ncbi Prosaposin is an AR-target gene and its neurotrophic domain upregulates AR expression and activity in prostate stromal cells
    S Koochekpour
    Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA
    J Cell Biochem 104:2272-85. 2008
    ....
  6. pmc Prosaposin down-modulation decreases metastatic prostate cancer cell adhesion, migration, and invasion
    Siyi Hu
    Stanley S Scott Cancer Center, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
    Mol Cancer 9:30. 2010
    ..PSAP is the lysosomal precursor of saposins, which serve as activators for lysosomal hydrolases involved in the degradation of ceramide (Cer) and other sphingolipids...