US Researchers Find Method to Block Cancer Stem Cell Differentiation

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 tumour-forming cells. This will allow researchers to further study and characterise 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 tumour cells because they are generally more resistant to standard chemotherapy and to conditions found inside tumours, such as low oxygen and acidity levels. Although they make up a relatively small portion of a tumour, cancer stem cells are believed to initiate and sustain tumours as they grow and metastasize. Cancer stem cells differentiate into other cells within three to five 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 tumour 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; Dr Prochownik and his team were 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. Dr Prochownik’s team at the Rangos Research
Center is now studying whether their method of blocking breast cancer stem cells also blocks those from other types of tumours. They also are screening large numbers of drugs to identify new ones that may be more effective against breast cancer stem cells. Other study authors include: Gangadharan B. Sajithlal, Ph.D, and Kristi Rothermund, Ph.D, Children’s Hospital; Fang Zhang, Ph.D, University of Pittsburgh School of Medicine; David J. Dabbs, Ph.D, Magee-Womens Hospital of UPMC; and Jean J. Lattimer, Ph.D, and Stephen G. Grant, Ph.D, University of Pittsburgh Cancer Institute and University of Pittsburgh School of Medicine.

*The report is published in the June issue of the journal Stem Cells.