Vascular stroma-derived endothelial colony forming progenitor cells adapt to tumour growth

Under appropriate nutrient agar culture conditions, primary or xenografted human and animal tumour biopsy-derived cell suspensions will form two types of colony. The first type, consisting of tight colonies of round cells which form tumours when introduced into nude mice, is of neoplastic origin. The second type of colony, the cells of which fail to form tumours on injection into nude mice, consists of loose colonies of larger, inter-connecting elongated bi- or tripolar cells and is thought to originate from vascular stroma-derived endothelial colony forming progenitor cells (V-ECPC). The likely importance of V-ECPC to tumour growth is emphasised by a positive correlation between the VECPC-derived endothelial cell colonies and both tumour vascularity and growth rate. A high cloning efficiency obtained from tumours of particularly intense vascular nature indicates that this cell is of importance in vascular adaptation and therefore tumour growth. In contrast, avascular, fibrotic tumour tissue yielded very low numbers of stromal vascular endothelial cell colonies. The results suggest that stromal vascular endothelial cell colonies do not arise from the mature fibroblastic elements of the tumour stroma, but rather from cells within actively growing regions. Tritiated thymidine uptake studies show that the vascular stroma-derived endothelial colony forming progenitor cells cell are cycling. Cell separation studies have characterized the as yet morphologically unidentified V-ECPC as having a sedimentation rate of 4.7 mm./hr and a mean density of 1.068 g/cm3 and hence a calculated volume of 450 microns 3.