Bone Marrow Microenvironmental Control of Prostate Cancer Skeletal Localization
Abstract
Prostate carcinoma metastasizes to skeletal sites where bone remodeling is active and engages the bone marrow niche in an unstable cascade with dysregulated bone resorption and formation. Numerous factors in the bone marrow niche have been implicated that support tumor growth. This proposal is focused on parathyroid hormone related protein (PTHrP), a tumor-derived factor that increases angiogenesis and enriches the bone marrow complement of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs). The overall hypothesis is that: Prostate cancer-derived PTHrP increases hematopoietic cells which in turn support tumor localization and growth in the bone marrow microenvironment. Two specific aims will validate this hypothesis using novel but well characterized animal models accompanied by in vitro cell biologic approaches. The first aim will determine the contribution of prostate cancer-derived PTHrP acting as a stem cell factor to facilitate prostate cancer residency in the bone microenvironment. Aim two will identify a pro-angiogenic impact of prostate cancer-derived PTHrP and elucidate its role in prostate carcinoma residency in the bone microenvironment. Prostate cancer lines expressing varying levels of PTHrP will be used in models where angiogenesis is measured and then altered to verify the PTHrP angiogenic response and dependence for the tumor impact on hematopoietic cells and the osteoblastic response.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2011
- Accession Number
- ADA561136
Entities
People
- Laurie Mccauley
Organizations
- University of Michigan