Objective: CD133(+) tumor cells are regarded as cancer stem cells (CSCs), responsible for tumor initiation, development, and relevant with chemo- and radio-resistance of tumors. However, how the destiny of CD133(+) cells is regulated by their niche remains largely unknown. In this study the interpretation of the relationship between CD133(+) cells and their niche were performed through investigating the distribution characteristics of CD133(+) cells in transplanted human glioma xenograft.
Methods: CD133(+) tumor cell spheres or tumor cells transfected with red fluorescent protein (RFP) gene were implanted in situ, subcutaneously or intraperitonealy in nude mice, then the xenografts were dissected and embedded in paraffin, stained with hematoxylin-eosin (HE), tumor tissues were further stained against CD133 with immunohistochemical and immunofluorescent techniques. The pathological structures of tumors and distribution characteristics of CD133(+) tumor cells were observed under microscope and confocal fluorescence microscope.
Results: Under microscope, distribution of CD133(+) glioma cells showed certain regularity and can be classified morphologically into three types: cell clusters, in pairs and single cells. Distribution of CD133(+) cells can also be classified according to their distribution location: accumulating around tumor vasculature areas, among the vascular endothelial cells, or in the normal brain tissue and ventricles. Under fluorescence microscope and laser confocal microscope, some of vascular endothelial cells inside the tumor region and some cells around tumor vessels co-express CD133 and RFP.
Conclusion: CD133(+) tumor cell clusters in nude mice are actually similar to those in CSCs spheres cultured in vitro. The single CD133(+) cells and CD133(+) cells in pairs represent asymmetric and symmetric division of CSCs within the CSCs niche, respectively. CD133(+) cells residing along tumor vessels are CSCs depending on CSC niche, and those locating far away from tumor blood vessels or tumor tissues, residing in normal brain tissues are the disseminated CSCs or neural stem cells which are not controlled or regulated by CSCs niche.