Effect of Physical Forces on the Metastatic Bone Microenvironment
Abstract
The overall goal of this project is to determine if prostate cancer (PCa) bone metastases increase intramedullary pressure (ImP). The central hypothesis to be tested is that tumors promote increased pressure thereby creating a more pro-tumorigenic environment. We have tested this hypothesis in vivo observing that tumors with an osteoblastic component do indeed lead to increased ImP. We have then utilized the pathologic pressures determined in vivo to perform in vitro experiments on PCa and bone cell lines. In vitro experiments have shown that increased pressure leads to decreased PCa proliferation. Osteoblasts also have inhibited proliferation, yet osteocytes have increased proliferation. Furthermore, conditioned media from osteocytes can promote an aggressive tumor phenotype when applied to tumor cells. Novel candidate genes with altered expression due to pressure have been identified and are currently undergoing further validation prior to functional testing. These results provide evidence that tumor induced pressure leads to a pro-tumorigenic environment and is the center of ongoing studies.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2013
- Accession Number
- ADA590462
Entities
People
- Joseph L. Sottnik
Organizations
- University of Michigan