Dissecting the Hierarchy of Tumor Cell Differentiation Using Dual Recombinase Technology in a Novel Mouse Model of Rhabdomyosarcoma

Background
One hallmark of cancer is that not all of the cells within a tumor are the same. For example, a subset of cancer cells called cancer stem cells may exist with a unique capacity to regenerate the tumor following therapy. If this is true, then identifying and killing these cells would be a new way to cure cancer. However, it has been difficult to test this cancer stem cell hypothesis because there has been no primary tumor model system where cancer stem cells and other unique populations of tumor cells can be tracked over time, evaluated for their response to treatment, and specifically deleted from the tumor.

We have recently developed a novel mouse model of embyronal rhabdomyosarcoma in which specific tumor cell populations within the primary cancer express proteins from normal muscle stem cells or mature muscle. Therefore, this model provides an unprecedented opportunity to label different populations of cancer cells expressing markers of different stages of normal muscle differentiation to define their role in the tumor.

Project Goal
I hypothesize that tumor cells expressing muscle stem cell markers will be the cancer stem cells and that they will be the key cell population required for tumor recurrence after cancer therapy. I will use genetic tools to delete these cells to determine if they are the key cells that must be killed to cure a sarcoma. These studies could have a major impact on the development of innovative treatments for both embryonal rhabdomyosarcoma and other cancers.