Do Prostate Cancer Exosomes Generate a Field Effect Leading to Tumor Multifocality?
Abstract
Prostates affected by cancer often not only contain one but multiple tumor sites. This is called multifocality or multifocal disease and complicates all aspects of prostate cancer clinical assessment and management. For example, it can bar the possibility of focal therapy, which is an increasingly developed and accepted organ-sparing approach through radiation, thermal therapy, and other interventions aimed at avoiding the side effects of prostatectomy. The development of focal therapy is part of the effort to develop personalized approaches for prostate cancer patients in the 21st century. In order to achieve this goal, it is mandatory to fully understand how multifocal disease develops, which is still a gap of knowledge. In this proposal, we combine two concepts of research in an attempt to fill this gap: "field effect" and "exosomes." Field effect denotes the presence of molecular alterations (mutations, upregulations, etc.) in structurally normal tissue adjacent to tumors, meaning at quite a distance from the tumor margins. Such fields are viewed by the pathologist as normal, but because of an altered molecular state, they could be prone to tumor formation. How such fields form is still unknown. Exosomes are microscopic vesicles that are shed by prostate cancer cells. These vesicles carry a multitude of factors that can influence cell function. We hypothesize for the first time that exosomes induce changes in cells at a distance from the tumor margin leading to the formation of fields that in turn lead to multifocal cancer. We propose to test this hypothesis with functional studies in cell models and observational studies in human tissues. If an association between exosomes and field can be established, it will pave the road for studies in mice with the aim to develop modes of intervention to inhibit the formation of multifocal tumors. We hope that in the future this will increase a patient s choice of therapies at the time of diagnosis with prostate cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510056
Entities
People
- Marco Bisoffi
Organizations
- Chapman University
- United States Army