Epigenetic Regulation of Chemokine Expression in Prostate Cancer
Annual rept. 1 Dec 2006-30 Nov 2007
PITTSBURGH UNIV PA
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Chemokines play an important role in initiating immune responses by regulating attraction and homing of immune cells to the lymphoid tissues. Breast and kidney-expressed chemokine BRAK CXCL14 is known to be selective for monocytes and dendritic cells DC. CXCL14 is expressed ubiquitously in normal tissues, but, as has been recently shown, absent in a variety of cancer tissues and tumor cell lines. However, the mechanisms responsible for CXCL14 loss in malignant tissues and cells are unknown. The main goal of this proposal is to determine the mechanisms of the regulation of CXCL14 expression by prostate cancer and test whether recovery of CXCL14 expression on tumor cells will be accomplished by attraction of DC and boosting of antitumor immune responses. During the first year of support, we evaluated chemoattractive properties of CXCL14 towards DC and demonstrated that human prostate cancer tissues and prostate cancer cell lines LNCaP, PC3, and DU145 do not express CXCL14 protein and mRNA and do not chemoattract DC in vitro and in vivo. The focus of Task 2 was to determine whether the restoration of CXCL14 expression on tumor cells might be associated with DC attraction in vitro and in vivo. Our data are briefly summarized below.
- Anatomy and Physiology
- Medicine and Medical Research