Oncogenic Role of 3-Mercaptopyruvate Sulfurtransferase in Endothelial Cells of the Tumor Microenvironment
Abstract
The 5-year survival rate for stage IV metastatic colorectal cancer is 13%. At this late stage, the cancer has already spread to other parts of the body, such as the liver, abdominal wall, and lung. It is now known that blood supply is essential for cancer cells to grow and spread aggressively, as it feeds the tumor with oxygen and nutrients and provides a route for cancer cells to spread to distant areas of the body. Cancer cells are able to create their own blood supply by activating surrounding vessel cells, namely endothelial cells. Current therapies for late-stage colorectal cancer aim to deprive tumors of their blood supply by preventing the development of new tumor blood vessels. However, patients often develop resistance to these treatments resulting in recurrence of cancer. Thus, better drug targets and improved understanding of tumor blood vessel formation are needed to develop new therapeutic strategies for colorectal cancer. Recently, our research group discovered that hydrogen sulfide (H2S), a gaseous signaling molecule, is abundantly produced in colon cancer cells and supports cancer cell growth and metastasis. Most importantly, H2S leads to new blood vessel formation in the tumor. This research focuses on understanding the role of H2S production by endothelial cells and its impact on tumor blood vessel formation. Specifically, we seek to determine whether selectively blocking the function of the H2S-producing enzyme, 3-mercaptopyruvate sulfurtransferase (3-MST) in endothelial cells surrounding the tumor will reduce the tumor blood supply, eliminating cancer cells from the colon and distant organs. Our preliminary findings suggest that 3-MST is a master regulator of tumor blood vessel formation. Therefore, we propose to elucidate the biological processes by which it supports tumor growth. Ultimately, the goal of this research is to explore and exploit 3-MST as a novel target for colorectal cancer therapy. CRC is a significant health problem for active military personnel, Veterans, and their families. Completion of the aims outlined in this proposal will provide a rationale for the development of novel therapeutic strategies that specifically target the 3-MST/H2S signaling pathway in patients with metastatic CRC. With the aid of the Peer Reviewed Cancer Research Program Career Development Award, Dr. Modis will establish herself as an independent investigator in the field of colorectal cancer research and becomes competitive for other funding opportunities.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010641
Entities
People
- Katalin Modis
Organizations
- United States Army
- University of Texas Medical Branch