H460 non-small cell lung cancer stem-like holoclones yield tumors with increased vascularity

Cancer stem-like cells were isolated from several human tumor cell lines by limiting dilution assays and holoclone morphology, followed by assessment of self-renewal capacity, tumor growth, vascularity, and blood perfusion. H460 holoclone-derived tumors grew slower than parental H460 tumors, but displayed significantly increased microvessel density and tumor blood perfusion. Microarray analysis identified 177 differentially regulated genes in the holoclone-derived tumors, of which 47 were associated with angiogenesis. The dysregulated genes include several small leucine-rich proteoglycans that may modulate angiogenesis and serve as novel therapeutic targets for inhibiting cancer stem cell-driven angiogenesis.