Stem and progenitor cells in brain ad breast malignancies

Abstract: Stem cells have qualities that clearly distinguish them from all other cells. Capabilities like self-renewal, differentiation and migration make them truly powerful. This thesis deals with different aspects of stem/progenitor cells in relation to cancer. Certain types of neural progenitor cells (NPCs) have been shown to possess a potential of tracking glioma cells in the brain. This makes them potentially very interesting as delivery vehicles in glioma therapy. In the first part of this thesis, we showed that certain NPCs have an ability of inhibiting tumor growth. We inoculated progenitor cells together with glioma cells in the nucleus caudatus of Fischer rats and saw a prolonged survival of the animals. We further demonstrated that we could enhance migration of these tumor-inhibitory NPCs to the site of glioma growth in a chemokine-dependent fashion. We introduced the chemokine receptor CXCR3 in the NPCs, and showed an enhanced migration of such overexpressing NPCs over the corpus callosum towards the glioma when inoculated at a distance from the tumor. In the second part of the thesis, we studied tumor-initiating cells in breast cancer. Tumors consist of a variety of cells with different features. A small population of cancer stem cells is believed to maintain this diversity. In breast cancer, a subpopulation of CD44+/CD24- cells is enriched for tumorigenic ability. We have stained human breast tumors for these markers and demonstrated a correlation of CD44+/CD24- tumor cells to basal-like and BRCA1 hereditary breast cancer. We also saw an increase of cells with the CD44+/CD24- phenotype when growing breast cancer cell lines with basal-like characteristics in non-adherent spherical clusters (mammospheres). Growing cells under such conditions enrich for cells with stem cell properties, as indicated by decreased proliferative rate and enhanced ability to generate new spheres from one single cell. We further showed an enhanced resistance to chemotherapeutic drugs for mammosphere-derived cells. In conclusion, stem and tumor cells seem to be linked in many ways, and increasing knowledge of their interactions could hopefully in the future lead to improved therapies against cancer.