Exploring cancer stem cell niche directed tumor growth.

The finding that only a sub-fraction of tumor cells, so called Cancer Stem Cells (CSC), is endowed with the capacity to initiate new tumors has important consequences for fundamental as well as clinical cancer research. Previously we established by computational modeling techniques that CSC driven tumor growth instigates infiltrative behavior, and perhaps most interesting, stimulates tumor cell heterogeneity. An important question that remains is to what extend CSC functions are intrinsically regulated or whether this capacity is orchestrated by the microenvironment, i.e. a putative CSC niche. Here we investigate how extrinsic regulation of CSC properties affects the characteristics of malignancies. We find that highly invasive growth in tumors dependent on a small subset of cells is not restricted to CSC-driven tumors, but is also observed in tumors where the CSC capacity of tumor cells is completely defined by the microenvironment. Importantly, also the high level of heterogeneity that was observed for CSC-driven tumors is preserved and partially even increased in malignancies with a microenvironmentally orchestrated CSC population. This indicates that invasive growth and high heterogeneity are fundamental properties of tumors fueled by a small population of tumor cells.