Exosome-Associated MTA1 in Breast Cancer Progression
Abstract
Metastatic breast cancer is responsible for the vast majority (90%) of breast cancer deaths. Therapies have been developed that can slow metastatic process, but none are able to cure metastasis. What drives this behavior in cancer cells is not well understood, which impedes our ability to develop new therapies targeted to this aspect of breast cancer. In recent years, a new appreciation of how cancer cells communicate through small, secreted vesicles has begun to take stage. These vesicles, called exosomes, are loaded with different factors from the cancer cell and secreted, where they can be absorbed by other cells within and surrounding the tumor. Cancer cell exosomes can also enter the blood stream where they can travel to distant organs and prime those organs for metastasis formation. However, the predominant factors present in exosomes that may contribute to this process are not well understood. We recently identified a cancer-related factor called metastasis-associated protein 1 (MTA1) in exosomes derived from breast cancer cells, breast ductal fluids, and breast cancer patient plasma samples. MTA1 is considered a master regulatory molecule associated with tumor progression due to its regulation of many cancer-promoting processes. In addition, MTA1 is highly expressed in many cancers, including breast cancer, which correlates with tumor metastatic metastasis progression. However, the precise role that MTA1 plays in promotion of cancer progression is not well understood. Furthermore, the utility of MTA1 as a blood-based biomarker of metastatic breast cancer has never been examined. Based on our preliminary data and the known functions of MTA1, we hypothesize that exosome-mediated transfer of MTA1 from breast cancer cells promotes breast cancer progression and can be utilized as a biomarker for metastatic breast cancer. The overall objective of this proposal is to identify the biological role and clinical utility of exosome-mediated transfer of MTA1 in breast cancer progression, which is well aligned with the current landscape of breast cancer research. This research aims to answer three basic questions: (1) Is MTA1 transferred by exosomes to specific cells surrounding the tumor and into the circulation? (2) Does exosome transfer of MTA1 contribute to metastatic progression of breast cancer? (3) Is there potential for MTA1 to be utilized as a biomarker for metastatic breast cancer? This proposal aims to address two overarching challenges identified by the Breast Cancer Research Program: (1) Identify why some breast cancers become metastatic. (2) Identify what drives breast cancer growth; determine how to stop it. Our overall goals with this project are to provide a basis for further development of MTA1 as a potential therapeutic target and predictive biomarker for metastatic breast cancer. Therefore, this project has the potential to help all breast cancer patients by providing a better way to identify patient metastatic status, and developing new strategies to target metastatic breast cancer. Specifically, the potential clinical applications for this proposal are that circulating exosome associated MTA1 may be developed as a potential indicator for metastatic breast cancer. Since MTA1 has crucial interactions with certain protein targets currently under clinical therapeutic evaluation, exosome-associated MTA1 is a potential therapeutic target against metastatic breast cancer. Upon completion of these studies circulating plasma exosome levels of MTA1 could be quickly implemented, once tested and validated, as a clinical biomarker of metastatic breast cancer. On the other hand, it may take some time to develop new anticancer agents targeting MTA1 or its interacting partners. In summary, because metastatic breast cancer is the cause for most breast cancer deaths, with this project we aim to discover new ways to identify and target metastatic breast cancer, which will have a significant impact on improving survi
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210317
Entities
People
- Wei-qun Ding
Organizations
- United States Army
- University of Oklahoma Health Sciences Center