DESCRIPTION (Provided by the applicant): Specific mechanisms of how the reactive microenvironment affects prostate cancer progression are
unknown. Previous studies from our group have shown that the reactive microenvironment has properties
and gene expression similar to wound repair biology. These include changes in stromal cell phenotype,
altered neurogenesis and the involvement of specific T regulatory cells. We have also shown that reactive
stroma is tumor promoting. These studies have shown that carcinoma cells and nerves exhibit reciprocal
interactions leading to elevated carcinoma proliferation and induced neurogenesis. In addition, the
involvement of gamma-sigma T regulatory cells may play an important role in tumor progression. The concurrent
recruitment of myofibroblasts to PIN and carcinoma foci implicates a coordinated host response in these
biologies that promotes tumorigenesis. Importantly, our group has shown that specific biomarkers of this
reactive microenvironment are predictive of recurrence of human prostate cancer. The integrated biologies
of this response and specific mechanisms are not yet understood at a level where more effective prognostics
or novel therapeutics can be developed. Accordingly, the overall objectives of this project are to understand
how reactive stroma, neurogenesis, and immunity responses in prostate cancer microenvironment function
and interact mechanistically during the initiation and progression of early, organ confined disease. The
endpoint of this study is to understand the key components, regulators, and mechanisms with a specific
focus on early prostate cancer. We have assembled a team of experts who will focus their efforts on
understanding three interrelated biologies in the tumor microenvironment. We propose a Program
composed of an Expression Analysis and Pathology Core and three interrelated Projects. Project 1 will
address the co-evolution, origin, and specific regulators of reactive stromal cells. Project .2 will address the
role of axonogenesis and neurogenesis in regulating early cancer. Project 3 will focus on the role of gamma-sigma T
regulatory cells and signaling through Toll-like receptors in prostate cancer progression. Together, these
Projects and Core will provide fundamental data regarding the temporal and spatial composition, gene
expression profiling, and potential regulators of the microenvironment in human tissues and mouse models.
This group of Investigators has worked together for several years and has planned these studies around
their pre-established collaborations. The overall goal of this Program is to provide novel pre-clinical data,
from which more effective biomarkers and therapeutics can be developed that target the microenvironment
of early prostate cancer.
PERFORMANCE SITE(S) (organization, city, state)
Baylor College of Medicine
Houston Texas
PHS 398 (Rev. 04/06) Page 2 Form Page 2
Principal Investigator/Program Director (Last, First, Middle): Rowley, David R., Ph.D.
KEY PERSONNEL. See instructions. Use continuation pages as needed to provide the required information in the format shown below.
Start with Principal Investigator(s). List all other key personnel in alphabetical order, last name first.
Name
Rowley, David R,
Rowley, David R.
Abd-EI-Fatta, ElMoataz
Ayala, Gustavo E.
Ayala, Gustavo E.
Chen, Wenhao (July, 2006)
Dai, Hong
Hilsenbeck, Susan G.
Hong, Jun (July 2006)
Ittman, Michael M.
Ittman, Michael M.
eRA Commons User Name
DROWLEY
DROWLEY
GAYALA
GAYALA
Shilsenbeck
Ittmann
Ittmann
Organization
Baylor College of Med.
Baylor College of Med.
Baylor College of Med.
Baylor College of Med.
Baylor College of Med.
Baylor College of Med.
Baylor College of Med.
Baylor College of Med.
Baylor College of Med.
Baylor College of Med.
Baylor College of Med.
Role on Project
Principal Investigator
Project Leader, P1
Research Associate, P2
Project Leader, P2
CORE Co-Leader
Postdoctoral Fellow, P3
Research Associate, P2
Co-Investigator, CORE
Postdoctoral Fellow, P3
CORE Leader
Collaborator, P2
OTHER SIGNIFICANT CONTRIBUTORS
Name
NA
Organization Role on Project |