Prostate cancer is tlie most frequently diagnosed non-cutaneous cancer and is the second leading cause of cancer death in American men. Stratifying patients with high-risl
Aim 2 will identify the role of inflammation on prostate cancer progression. Tgfbr2'*'"^? prostates that develop into adenocarcinoma will be grafted with stromal cells that express CX3CL1, CCL4 and IL-15. Bone marrow derived cells that are recruited to the prostate will be identified and quantified. Chimeric mice with bone marrow derived cells knocked out for the expression of the primary CX3CL1 receptor and CCL4 receptor will be developed. The goal will be to characterize the consequences of ablating the recruitment of specific populations of inflammatory cells to the prostate.
In Aim 3 prostate cancer cell lines expressing CX3CL1, CCL4 and IL-15 will be treated with curcumin to determine whether curcumin can inhibit metastasis of prostate cancer in vitro through the regulation of CX3CL1, CCL4 and IL-15. Xenograft tumor models will test whether curcumin modulates tumor metastasis in vivo through the regulation of CX3CL1, CCL4 and IL-15. These results will provide biologic basis for the clinical use of the chemokine biomarkers and development of new therapies aimed to inhibit prostate cancer metastasis.
The early determination of metastatic prostate cancer can enable appropriate treatment and save patients who would eventually die of recurrence of prostate cancer. The proposed research will determine the function of predictive chemokines and curcumin in prostate cancer metastasis. This might allow for the future development of new therapies aimed to inhibit the growth and spread of prostate cancer tumors.