Tumors exposed to acute cyclic hypoxia show increased vessel density and delayed blood supply

Abstract

The purpose of this study was to investigate the effect of acute cyclic hypoxia on tumor vasculature. A-07 human melanoma xenografts growing in dorsal window chambers were used as tumor model. Acute cyclic hypoxia was induced by periodically exposing tumor-bearing mice to a low oxygen atmosphere. The hypoxia treatment consisted of 12cycles of 10min of low O2 (8% O2 in N2) followed by 10min of air for a total of 4hr. The treatment started the first day after tumor initiation, and was given daily for 9days. Vascular morphology was assessed from high-resolution transillumination images, and tumor blood supply was assessed from first-pass imaging movies recorded after a bolus of 155kDa tetramethylrhodamine isothiocyanate-labeled dextran had been administered intravenously. Hypoxia-treated tumors showed increased vessel density, decreased interstitial distance, and delayed blood supply compared to control tumors. The increase in vessel density was attributed to an increased number of small vessels. In conclusion, acute cyclic hypoxia induced angiogenesis in A-07 tumors resulting in increased density of small-diameter vessels and delayed tumor blood supply.