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.
Dr. Sarah Stuckelberger is a postdoctoral fellow in the laboratory of Dr. Ronny Drapkin at Ovarian Cancer Research Center at the University of Pennsylvania in Philadelphia. Dr. Stuckelberger earned her MD from the University of Geneva, Switzerland, in 2012, and is currently a resident in Gynecology and Obstetrics at the Lausanne University Hospital. She joined Dr. Drapkin’s laboratory a year ago, after receiving awards from two Swiss Foundations (The Stanley Park Foundation and the Fondation pour le perfectionnement et la recherche en gynécologie et obstétrique du Centre Hospitalier Universitaire Vaudois). Her studies focus on developing a new mouse model to study the susceptibility of the fallopian tube epithelium to neoplastic transformation. Although a number of human cell line models have been developed, there are currently no murine fallopian tube-derived cell lines are available for cancer research. This new syngeneic model will allow the implantation of transformed mouse fallopian tube cells into immunocompetent mice to study how the host microenvironment interacts with the tumor, and to test new emerging immunotherapies. Such a model would represent a renewable resource for the ovarian cancer research community.