Pamela K Kreeger, Ph.D.
University of Wisconsin-Madison
Madison, WI, United States
Project: Role of P-selectin in transcoelomic spread of ovarian cancer
Research Area: Cancer Biology, Novel Therapy
In high grade serous ovarian cancer, metastasis or spread of the cancer occurs when tumor cells break away from the primary tumor, float through the fluid in the abdominal cavity, and attach to the lining of tissues in the abdomen to form new metastases. Blocking tumor cell attachment could slow or stop the development of additional metastases and improve patient outcomes and quality of life. Dr. Kreeger’s lab has analyzed the role of a population of immune system cells, called the alternatively-activated macrophages, in this process. Through their experiments, they have determined that these macrophages produce a substance called MIP-1ß that increases the level of another protein called P-selectin on the cells that line the abdominal cavity. In a bioengineered experimental model Dr. Kreeger tested, the P-selectin protein allows tumor cells to attach and ‘stick’. Excitingly, there are already drugs that are approved by the Federal Drug Administration to inhibit the receptor for MIP-1ß or in clinical trials to inhibit P-selectin. While these drugs were developed for diseases other than cancer, they could potentially be used to control metastasis in ovarian cancer. In this project, Dr. Kreeger will validate that P-selectin promotes metastasis in mouse models of high grade serous ovarian cancer in order to move forward with pre-clinical testing of those drugs and ultimate translation to the treatment of patients in the clinic.