Notch Signaling in Prostate Cancer Cells Promotes Osteoblastic Metastasis
Abstract
Scientific Objective and Rationale: Prostate cancer (PCa), the most common non-skin cancer, is the second leading cause of cancer death in men worldwide. Most PCa deaths are due to bone metastases. PCa invariably metastasizes to the bone and causes abnormal bone formation (osteoblastic lesions). This results in unbearable pain, spinal nerve compression, and eventual death. What triggers PCa metastasis to the bone and what causes osteoblastic lesions remain unanswered. Death from metastatic bone disease is due in part to the lack of effective therapies, the development of which requires knowing the signaling pathways that lead to this osteoblastic phenotype. The proposed project will determine how prostate cancer cells when residing in the bone will influence its surroundings, called the bone tumor microenvironment, in the formation of osteoblastic metastasis. Our preliminary data suggest that Notch signaling, known for its role in influencing the tissue microenvironment during development, can promote the formation of osteoblastic lesions. This project will test the hypothesis that Notch signaling in cancer cells promotes secretion of factors that induce osteoblastic lesions by increasing the proliferation of bone forming cells (osteoblasts) while simultaneously inhibiting bone degrading cells (osteoclasts). Career Goals in Prostate Cancer Research: My ultimate career goal is to establish my own research laboratory focused on elucidating the mechanisms of PCa bone metastasis with the goal of contributing to PCa patient s survival and quality of life. At the same time, I want to be actively involved in education so that I can pass on my research expertise to the next generation of scientists. To reach my goals, I have carefully selected the research environment, including the institute and the mentors for my post-doc training as the first step. My mentors and I have established and implemented an individual career development plan since the time I started the training. I have already moved forward with my plan by publishing a review paper summarizing the relevant published findings in PCa bone metastasis and working towards a peer reviewed research paper. In addition, I am submitting grant applications to support my research project. If my proposal is funded, the training plan I proposed here will further help me achieve my goals. The proposed project, on PCa bone metastasis, requires I understand the biology of PCa and how PCa cells interact with the bone to promote metastasis. Both my mentors have different expertise in PCa and bone metastasis, which will help me gain the needed understanding and skills to successfully carry out the project. My training program also takes advantage of ongoing programs within the institute, which includes interactions with other researchers, with expertise in PCa and bone biology and participation in research group meetings, research seminars and journal clubs, annual research conferences and institutional retreats. To further enhance my knowledge and bring applicability to my research, I will also take some courses offered by the institute, like Biostatistics, grant and manuscript writing courses. In addition, I have also initiated collaboration with Dr. Evan Keller, a recognized expert in the field of PCa-induced bone metastasis and Dr. Kurt Hankenson, an established scientist who will serve as an expert on Notch in the bone microenvironment. Both these collaborators expertise will help me in my project. These types of interactions and events will facilitate my career development. Overall, the proposed postdoctoral training is crucial for me to fulfill my career ambitions. Applicability and Impact of Research: Results obtained from the proposed study will open the doors for future development of new therapies for PCa patient with metastatic disease by targeting both the cancer cells and the associated bone microenvironment. Targeting the bone microenvironment
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610136
Entities
People
- Sourik Ganguly
Organizations
- United States Army
- Van Andel Institute