Neuronal Function and Incurable Prostate Cancer
Abstract
In spite of much knowledge on the role of tumor neuron interactions in primary prostate cancer, the role of neurons in metastatic prostate cancer is not understood at present. This is an unmet need because it is clear that neurons are able to exert control over many essential functions of tissues that are commonly suffering metastatic PC colonization. These include physiological functions including control of blood pressure, digestion, pain and stress responses, to name a few. Here we combine the synergistic and complementary expertise of three scientists to make fundamental inroads into understanding how neurons affect death from metastatic castration-resistant prostate cancer. Dr. Loda at Weill Cornell Medical College has developed three-dimensional imaging of samples that are many centimeters thick. This overcomes the limitation of classic imaging where sample thickness is a few thousandths of a millimeter so that axons, which project from nerves to their target cells, can possibly be traced. At the same time, in mouse, Dr. Trotman (CSHL) has also developed three-dimensional imaging of samples by adapting two techniques (two-photon tomography and tissue clearing) that have previously only been used on mouse brains, but not on organs that are invaded by metastatic PC. Finally, Drs. Borniger and Trotman have developed a tissue culture platform called the Xona Chip, where interactions between axons from relevant neurons and metastatic prostate cancer cells can be dissected at the molecular level. Together, the team will now map the type and architecture of nerve cells that interact with metastatic PC cells in patients and in the mouse models in their first Aim. In the second Aim, they will ask what the functional relevance of any interaction is, using the Xona Chip and the molecular manipulation of mouse and human metastatic cancer cells and neurons that it facilitates, as well as mouse models where neurons can be activated or silenced in mice that carry metastatic prostate cancer. In the long run, this research leads to programs for defining whether and how discrete neuronal-metastatic cancer modulators (for a random example, drugs like beta beta-blockers) can harm or benefit patients with metastatic castration-resistant PC. These results are of high clinical importance because many metastatic prostate cancer patients are taking neuro-modulating drugs for various and not necessarily cancer-related reasons.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210871
Entities
People
- Lloyd Trotman
Organizations
- Cold Spring Harbor Laboratory
- United States Army