McGowan Institute for Regenerative Medicine
affiliated faculty member Jean Latimer, Ph.D. (pictured), assistant professor at the University of Pittsburgh in the Department of Obstetrics, Gynecology and Women’s Health, and also a faculty member in the Cellular and Molecular Pathology Graduate Training Program and the University of Pittsburgh Cancer Institute, along with a team of scientists from Children’s Hospital of Pittsburgh of UPMC and the University of Pittsburgh School of Medicine have discovered an unprecedented method of permanently blocking cancer stem cells so they remain stem cells instead of differentiating into other types of tumor-forming cells. The discovery is significant because it will allow researchers to further study and characterize cancer stem cells, as well as screen drugs that could specifically target them.
The research, which involved four different lines of breast cancer stem cells, was led by Edward Prochownik, M.D., Ph.D., director of Oncology Research at Children’s Hospital and the Paul C. Gaffney Professor of Pediatrics and of Molecular Genetics and Biochemistry at the University of Pittsburgh School of Medicine.
Cancer stem cells are heartier than other types of tumor cells because they are generally more resistant to standard chemotherapy and to conditions found inside tumors, such as low oxygen and acidity levels. Although they make up a relatively small portion of a tumor, cancer stem cells are believed to initiate and sustain tumors as they grow and metastasize.
Cancer stem cells differentiate into other cells within 3 to 5 weeks of being isolated, making them difficult to study, according to Dr. Prochownik. He and his colleagues at the John G. Rangos Sr. Research Center at Children’s Hospital were able to tag the breast cancer stem cells they isolated with green fluorescent protein and a stem cell-specific promoter know as Oct3/4.
“Using this approach, we can essentially freeze the stem cells in their current state, grow them in unlimited quantities and then study them at our leisure so we’ll be able to understand what makes cancer stem cells more efficient than other types of cancer cells,” Dr. Prochownik said. “More importantly, having this unlimited supply of cancer stem cells allows us to use existing technology to screen them for chemotherapy agents and other therapies to determine which therapies are most effective at destroying the cancer stem cells. The goal is an arsenal of therapies to target both the tumor as a whole as well as those specific to the cancer stem cells.”
The discovery of how to block these cancer stem cells was serendipitous; the team was initially trying to develop a way to track the cancer stem cells to determine what other types of cells they differentiated into and how long the process takes. Now, the team at the Rangos Research Center is studying whether their method of blocking breast cancer stem cells also blocks those from other types of tumors. They also are screening large numbers of drugs to identify new ones that may be more effective against breast cancer stem cells.
Illustration: McGowan Institute for Regenerative Medicine.
University of Pittsburgh Schools of the Health Sciences Media Relations News Release (05/27/10)
Children’s Hospital of Pittsburgh of UPMC News Release (05/27/10)
UPMC Cancer Centers News Release (05/27/10)
Bio: Dr. Jean Latimer
Abstract (Stem Cells. 2010 Apr 7.)