The Impact of the Dura Mater on Prostate Spine Metastases
Abstract
Cancer can spread to nearly all tissues of the body; one of the most common sites of spread is to the bones. Nearly 300,000 adults in the United States currently have osseous metastatic disease, with approximately 63,000 men living with bone metastases from prostate cancer. The majority of these metastases are found in the spine. About two-thirds of all symptomatic bone metastases are located in the spine, with up to 74% of patients having spine metastases at autopsy, and a majority of these are in the posterior part of the vertebral body. Spinal metastases are a large contributor to cancer pain and subsequent disability as a result of tumor growth and spinal cord compression. Although the odds of a prolonged life with cancer have improved in recent years, this complication of malignancy leads to enormous health care costs upwards of $100,000 per patient per incident. There is a critical gap in understanding why cancers grow better in the spine. The “Seed and Soil” theory, postulated long ago by Paget, is still valid today. This theory posits that the process of colonization and growth requires an interaction between the tumor cells and the microenvironment. Differences in the local microenvironment lead to differential tumor dispersion and growth. This is most prominently seen in ecology with invasive species. A species will barely survive in one environment, but put it in another environment, and it will grow out of control. This is similar to cancer. Understanding the environment that allows this growth can lead to interventions that stop the growth. Here, we seek to gain an understanding of one aspect of the spine environment where prostate cancer grows so well. A key feature of the spinal skeleton local environment is the proximity of the dura mater adjacent to the posterior aspect of the vertebral body, the covering of the central nervous system. The dura may serve as a critical structure that interacts with the local bone microenvironment and with metastatic tumor cells contributing to the preferential metastatic growth in the spine. The immediate objective is to examine the dura and its effects on prostate cancer cells, as well as the effect of tumor cells on the dura. Tumor cells change the environment to help themselves grow; we will examine this feedback loop and ways of blocking it. Because the dura is next to the vertebral body, we look to molecules that the dura releases. These molecules act as keys that unlock doors to pathways that increase tumor malignancy and growth. We will use different methods to quantify the effect and determine the clinical significance of these keys in animal models. We have identified possible targets via preliminary work, and we will use techniques to change the locks on the doors of the cancer cells to see whether there is clinical benefit. If this results in less tumor growth in animal models, then we know that the next step is for human trials. The ultimate application of this research is far-reaching. In the short term, it will give us insight into the spine microenvironment and what role the dura plays in modulating this environment to help the growth of prostate cancer cells. It will also tell us whether blocking these receptors has clinical significance. The long-term application is much broader. The factors that help prostate cancer grow in the spine may be common to all spine metastases. We have seen similar findings to our preliminary data in other spine cancers. These results could be applied to all cancer patients to stop the cancer from going to the spine. This would have a huge impact on all cancer patients. The results have the potential to be utilized in many different types of patients. In prostate cancer patients with an initial diagnosis of cancer, this pathway could be blocked and decrease the rate of metastases (the environment would not be conducive to growth; thus, even though cells get there, they cannot survive in the verte
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810487
Entities
People
- Nicholas J. Szerlip
Organizations
- United States Army
- University of Michigan