BBB seminar: Rolf Bjerkvig
Cancer and cancer stem cells
Department of Biomedicine, University of Bergen
The molecular events that lead to the cancer-initiating cell (cancer stem cell) involve critical mutations in genes regulating normal cell growth and differentiation. Cancer stem cells have been described in the context of acute myeloid leukemia, breast, bone and brain cancers. These cells have been shown to be critical in tumor development and should harbor the mutations needed to initiate a tumor. The host microenvironment has been shown to play an important role in tumor progression and there is an increasing body of evidence showing that the surrounding stroma not only supports tumor growth and invasion, but also has a direct role in tumorigenesis, by acting as a mutagen. The origin of cancer stem cells is not clear. They may be derived from stem cell pools, progenitor cells, differentiated cells or somatic cells that undergo trans-differentiation processes.
It has been suggested that cell fusion and horizontal gene-transfer events, which may occur in tissue repair processes, also might play an important role in tumor initiation and progression. Fusion between somatic cells that have undergone a set of specific mutations, and normal stem cells might well explain the extensive chromosomal derangements seen in early tumors. This event might represent the underlying source for the development of the cancer stem cell that eventually initiates a tumor. Major challenges will be to identify and characterize the tumor-initiating cells and to determine how they differ from normal stem cells. By the identification of such differences, novel targets leading to the development of new tumor therapies can be identified.