Ovarian cancer is the fifth deadliest cancer among women in developed countries. Worldwide, nearly a quarter of a million women will be diagnosed with this disease each year. It is a devastating disease, as the majority of cases are discovered too late for efficient treatments. The most common subtype of ovarian cancer is called high-grade serous cancer (HGSC). For years, people thought that these tumors came from the ovary. We now believe that many of these cancers originate in the very tips of the fallopian tubes called the fimbria. In order to better understand the mechanisms that allow ovarian cancer to start and spread, researchers have created different models to mimic the development of human ovarian cancer. Many of the ovarian cancer models consist of cells, coming from human fallopian tubes that are transformed into tumors through genetic manipulations. The tumorigenic cells can be grown in the laboratory (in vitro) before being grown in a mouse (in vivo). These models are very useful, but they have limitations. In order for transformed human fallopian tube cells to grow and create a tumor in a mouse, the mouse needs to be immunocompromised. Meaning, that is does not have an immune system. In this way, a mouse lacking an immune system will not be able to “recognize” the human cells as foreign and reject them. This type of model system precludes our ability to study the interplay between the tumor cells and the microenvironment. There is currently no mouse fallopian tube cell line that can be transformed into a HGSC and studied in an immune competent mouse. This is particularly important since mounting evidence show that our immune system can influence tumor growth.
The goal of my project is to develop a new model using mouse fallopian tube cells. These cells will be multiplied and transformed into a tumor in vitro. We will then inject them into a same species mouse that is immune competent. By doing so, we will be able to monitor how the immune system reacts to the tumor and how tumors can evade the immune system. More importantly, this model will let us test new emerging immunotherapies that reactivate the immune system. Successful generation of this model will represent a renewable resource for the ovarian cancer research community.
This grant was made possible by a generous donation from the Sandy Rollman Ovarian Cancer Foundation, and The Teal Foundation.