Tumor cell spheroids induce a mitogenic response in endothelial cells

Conditioned media from spheroids of human colorectal tumor cell lines HT29, SW620, SW480 and CaCo-2 were tested for their mitogenic activity on human umbilical vein endothelial (HUVE) and bovine capillary endothelial (BCE) cells. All spheroid-conditioned media were capable of increasing the labeling indices in both endothelial cell populations, with the mitogenic activity decreasing in the following order: SW620, HT29/SW480 and CaCo-2. The endothelial cell mitogenic activity of the spheroids was not dependent on the presence of necrosis nor on their in vivo cytokinetic characteristics. We conclude that tumor spheroids release mitogenic activity for endothelial cells, but this stimulation depends on the age of the tumor spheroid as well as on the type of tumor used.