Prostate Cancer Scientific Abstracts - M. Aalamian

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Selected M. Aalamian prostate cancer abstracts

Journal: J Urol

Pubmed ID: 14532846

Authors: Aalamian M, Tourkova IL, Chatta GS, Lilja H, Huland E, Huland H, Shurin GV, Shurin MR.

Title: Inhibition of dendropoiesis by tumor derived and purified prostate specific antigen.

PURPOSE: Prostate specific antigen is a serine protease produced by the prostate gland at high concentrations. Serum prostate specific antigen may be significantly elevated in prostate cancer and benign prostatic diseases. It has recently become evident that, in addition to being a tissue and/or serum marker, Prostate specific antigen may also have biological effects. Despite the voluminous literature on this biomarker in the diagnosis of prostatic diseases relatively few reports have addressed the issue of the physiological function, biological role and immune effects of Prostate specific antigen in the context of prostate cancer development and progression.

MATERIALS AND METHODS: Human dendritic cell (DC) cultures were generated from CD34+ hematopoietic precursors in the presence of prostate specific antigen. The DC phenotype was assessed by flow cytometry and DC ability to induce T-cell proliferation was detected by allogeneic mixed lymphocyte reaction assay. DCs were also generated in co-cultures with LNCaP cells in the presence of antiPSA antibodies. The concentrations of PSA in cultures were determined by the AXSYM System (Abbott Laboratories, Wiesbaden , Germany ).

RESULTS: We noted that purified and LNCaP derived PSA inhibited the generation and maturation of DC (dendropoiesis) in vitro, which might have a crucial role in the induction and regulation of specific antitumor immune responses. The addition of active PSA to DC cultures significantly inhibited the generation and maturation of DC, as assessed by the levels of expression of CD83, CD80, CD86 and HLA DR. The ability of DC to induce T-cell proliferation, which depends on the expression of co-stimulatory and major histocompatibility complex molecules, was also suppressed in Prostate specific antigen treated DC cultures.

CONCLUSIONS: The antidendropoietic effect of Prostate specific antigen in vitro suggests a new mechanism of prostate cancer induced immunosuppression and tumor escape, and provides novel evidence of the immunoregulatory properties of Prostate specific antigen.

Contact: Department of Urology, University Clinics Hamburg-Eppendorf, Hamburg, Germany.

 

Journal: Prostate

Pubmed ID: 11170134

Authors: Aalamian M, Pirtskhalaishvili G, Nunez A, Esche C, Shurin GV, Huland E, Huland H, Shurin MR.

Title: Human prostate cancer regulates generation and maturation of monocyte-derived dendritic cells.

BACKGROUND: The progression of prostate cancer is accompanied by a marked suppression of the immune system, including the apoptotic death of dendritic cells responsible for the induction of antitumor immunity. In this study, we evaluated whether prostate cancer might inhibit dendritic cells generation and maturation in vitro.

METHODS: dendritic cells were generated from peripheral blood monocytes in the presence of the human prostate cell line LNCaP or nonmalignant cells, and characterized by light microscopy, FACScan analysis, and ability to stimulate T-cell proliferation.

RESULTS: Prostate cancer significantly inhibited the conversion of monocytes into dendritic cells, which was assessed by the expression of dendritic cells markers CD1a and CD83. These cells were weak stimulators of T-cell proliferation, suggesting that dendritic cells generated in the prostate cancer microenvironment are functionally inhibited.

CONCLUSIONS: Prostate cancer not only kills mature DC, but also inhibits their generation and maturation, resulting in decreased production of antigen-presenting cells and inhibition of their functional activity.

Contact: Department of Urology, University Clinics Hamburg-Eppendorf, Hamburg, Germany.


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