Accession Number : ADA580499

Title :   Regulation of the Prostate Cancer Tumor Microenvironment

Descriptive Note : Annual summary 15 Mar 2012-14 Mar 2013

Corporate Author : CALIFORNIA UNIV LOS ANGELES

Personal Author(s) : Chin, Arnold I

Full Text : http://www.dtic.mil/dtic/tr/fulltext/u2/a580499.pdf

Report Date : Apr 2013

Pagination or Media Count : 13

Abstract : The role of innate immunity in prostate cancer tumorigenesis is unclear. Toll-like receptors (TLRs) are key signaling molecules that regulate innate and adaptive immune responses in the presence of pathogens and endogenous ligands. During our first two years of this training proposal, we have generated and begun to characterize TRAMP Tg+/- x MyD88-/- mice. Initial results reveal that de novo prostate cancers in absence of MyD88 are larger with higher grade adenocarcinomas than wild-type controls at 30 weeks of age. Analysis of tumor infiltrating cells at 24 weeks of age already reveal increased infiltration of macrophage lineage cells and decreased T lymphocytes, as well as decreased activation of canonical NF- B levels and increased non-canonical NF- B levels in the MyD88-deficient TRAMP Tg+/- mice. We have also observed decreased splenocytic NK cells in MyD88-/- animals with and without the presence of prostate cancer. From these data, we will determine the role of the MyD88 pathway of innate immunity in prostate cancer tumorigenesis. However, we have noted several limitations of our current system in achieving our initial aims. Thus, we have also recommended proposed changes to better address our hypothesis subject to the approval of the Dod.

Descriptors :   *PROSTATE CANCER , NEOPLASMS , PATHOGENIC MICROORGANISMS , RESPONSE(BIOLOGY) , T LYMPHOCYTES

Subject Categories : Anatomy and Physiology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE