Date of Award

12-1-2007

Degree Type

Thesis

University or Center

Clark Atlanta University(CAU)

School

School of Arts and Sciences

Degree Name

M.S.

Department

Biology

First Advisor

Dr. Godwin A. Ananaba

Second Advisor

Dr. Nathan Jideama

Third Advisor

Dr. Jaideep Chaudhary

Abstract

Anti-inflammatory specific cytokines and chemokines are elevated in many advanced tumors and correlate with poor prognosis. However, the differential expression of anti-inflammatory cytokines and chemokines in prostate cancer is not known. We investigated the hypotheses that androgen unresponsive DU145 and PC3 prostate cancer cells and androgen responsive LNCaP prostate cancer cells, differentially expressed selected anti-inflammatory and pro-inflammatory cytokines and chemokines and that, dendritic cells pulsed with prostate tumor antigens will induce mainly pro-inflammatory cytokines and chemokines in T cells using mouse models. Our results indicated that anti-inflammatory specific cytokines IL-1 0, IL-4, and anti-inflammatory specific chemokine CCL- 17 (TARC) and cognate receptor CCR4 are expressed in prostate cancer cell lines. Quantitative real-time PCR (qRT-PCR) revealed an almost five-fold increase in chemokine CCL17 and its cognate receptor CCR4 mRNA in androgen unresponsive DU145 and PC3 prostate cancer cell lines compared to androgen responsive prostate tumor LNCaP. Protein analysis indicated significantly increased secretion of anti-inflammatory cytokine IL- 10 by DU145 and PC3 compared to LNCaP. Furthermore, pro-inflammatory cytokine IFN-y and pro-inflammatory chemokine IP- 10 secretion were significantly less in these prostate cancer cells, when compared to immortalized normal prostate epithelial cells. Our in- vivo analysis revealed that T cells were activated by pulsed dendritic cells shown in the increase mRNA expression of pro-inflammatory cytokine IFN-y and pro-inflammatory chemokine IP- 10, and cognate receptor CXCR3. However, a predominant pro-inflammatory response was not observed as anti-inflammatory cytokines and chemokines were also seen. The production of anti-inflammatory cytokines and chemokines suggests a possible mechanism for prostate cancer to evade host immune responses by negatively modulating immune responses that are necessary for destroying cancers cells.. Cytokine and chemokine profiles could be used as potential prognostic markers for disease progression. Additionally, an effacious vaccine will depend on its ability to inhibit the recruitment of known distinct functional anti-inflammatory effector molecules, implicated in prostate cancer progression.

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