A New Paradigm for Ovarian Sex Cord-Stromal Tumor Development
Abstract
In the ovarian cancer research field, efforts are narrowly and predominantly focused on the main type of ovarian cancers (i.e., tumors from epithelial cell origin). Little is known about the cause of sex cord-stromal tumors, which account for ~8% of ovarian cancers. Unlike the main type of ovarian cancer, these tumors are derived from the stromal compartment of the ovary instead of epithelial cells. Because of the poorly understood cause, there are no effective treatments for these tumors in the clinics. Transgenic mouse models are among the most powerful tools for cancer research. The available models focus on abnormal changes in ovarian cancer cells per se, and little is known about the role of their neighbors (i.e., cells that interact with cancer cells). Increasing evidence shows that these neighboring cells may play very important roles in cancer development. In the ovary, the functional unit is a follicle, which contains granulosa cells (i.e., the origin of sex cord-stromal tumors) and an egg or oocyte (an important neighboring cell). The question we ask is: Does the egg play a role in ovarian cancer development? To answer this question, we created a mouse model that has increased activity of a growth factor called transforming growth factor-beta specifically in the oocytes. This growth factor family has been shown to be critical for cancer development, and we have learned many of their roles in female reproduction from our previous studies. We were surprised that these mice developed ovarian sex cord-stromal tumors. This finding strongly indicates that the oocyte could be an important player in the development of this type of ovarian cancers. Therefore, we have created a novel mouse model that can be used to investigate how sex cord-stromal tumor develops from a completely new perspective. Our overall objective for this proposal is to investigate how increased growth factor activity in the oocyte causes ovarian cancer development. The rationale is that by defining how ovarian cancer initiates in our mouse model, we expect to identify novel regulators of the egg-granulosa cell interaction, the alteration of which leads to cancer development. Thus, the central problem that will be addressed is to establish a new paradigm for sex cord-stromal tumor development and discover new targets for their early detection and treatment. To attain our objective, we will use multiple approaches and perform a series of carefully controlled studies. Successful completion of these studies is expected to discover a previously unrecognized novel route for ovarian sex cord-stromal tumor development. Therefore, our proposal holds promise to aid in the design of new treatment approach for these poorly understood tumors. With a strong aim to identify novel targets for early ovarian cancer detection and treatment, our proposal is aligned very well with the mission of Ovarian Cancer Research Program (OCRP). Our application fits in with two priority areas of OCRP, which are to understand cancer microenvironment and pathogenesis/progression and validate models to study ovarian cancer initiation/progression. Military Service members and their families suffer from more emotional and physical burden of the ovarian cancer, a leading cause of death in women. By identifying novel targets for early detection and treatment of ovarian cancers, our proposed studies are expected to have a positive impact on the health and welfare of Military Service members and their families. With all essential expertise, resources, and enthusiasm, our team is uniquely positioned to perform the proposed studies. It is our expectation that new breakthroughs will be made in ovarian cancer detection, prevention, and treatment, which will help reduce the pain and suffering of ovarian cancer patients and their families.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510082
Entities
People
- Qinglei Li
Organizations
- Texas A&M University
- United States Army