) This proposal is written in response to RFACA 93-037 entitled """"""""Role of Microenvironment in Breast and Prostate Cancer"""""""", an area of research to which the Principal Investigator has devoted much of his effort in the past decade. To define the prostate tumor microenvironment, this proposal focuses on stromal-epithelial interaction in prostate cancer growth, progression and differentiation. Specifically, we propose to examine the biology of human prostate cancer metastasis using a novel model developed in our laboratory. In this model, a LNCaP subline C4-2 derived from bone stroma prostate cancer cell (LNCaP) interaction in castrated mice acquired androgen-independence (when grown in castrated host) and metastatic potential (from primary-lymph node-bone). We propose to investigate in detail the molecular and biochemical mechanisms that are associated with the multistage prostate cancer progression. A multidisciplinary approach will be taken to evaluate the genetic changes of the cancer epithelium associated with tumor progression. An effort will be made to characterize the soluble growth factors and the bone matrix-associated proteins that may be involved in distant metastasis. The relevance of the factors identified in the experimental model to those associated with either early or late phases of human prostate cancer progression will be evaluated using clinical samples.
