Tumor Microenvironment Network (TMEN): Reactive Stroma and Tumor Associated Macrophages in Prostate Cancer
The specific mechanisms of how the microenvironment regulates prostate cancer progression remain poorly understood. The combined previous studies of Drs. Pienta and Rowley have revealed that tumor associated macrophages (TAMs) and reactive stroma both promote prostate cancer progression. Dr. Pienta has demonstrated a major role for CCL2 in prostate tumor growth and metastasis through its regulatory role in mediating monocyte / macrophage infiltration into the tumor microenvironment and stimulating a phenotypic change to TAMs within these immune cells to promote tumor growth. Dr. Rowley has demonstrated that human prostate cancer reactive stroma is composed of myofibroblasts that initiate during PINand continually co-evolve with adjacent carcinoma during organ-confined progression. The overall hypothesis of this application is that TAMs and reactive stroma serve as complementary coregulators of each other and together promote prostate cancer growth in primary and metastatic sites. These Aims will use the extensive set of human normal and prostate cancer samples in theBaylorUniversity andUniversity ofMichigan SPORE Tissue Banks, including samples obtained through the rapid autopsy program and samples from the mouse models of prostate cancer growth in primary prostate and bone.
Central Question 1: What is the relationship between TAMs and the development of reactive stroma myofibroblasts?
Specific Aim 1: Define the mechanisms by which TAMs promote myofibroblast differentiation and function. This Aim will determine:
Central Question 2: What is the composition of human prostate cancer reactive stroma?
Specific Aim 2: To determine the composition of reactive stroma within prostate cancer bone metastases.
Rowley lab: http://www.bcm.edu/mcb/?PMID=7692