Effects of Cyclic Hypoxia in Tumor Tissue.

Abstract

The presence of hypoxia in tumors has been related to poor prognosis and low overall survival. In particular, cyclic hypoxia has been related to higher metastatic potential. Hence, it is important to study the mechanisms involved in the response of tumors when these experience cyclic hypoxia. In this work A-07-GFP human melanoma xenografts with dorsal window chambers were used as a model to study the effects of exposure to cyclic hypoxia on tumor growth and on the morphology and function of the tumor vascular networks. First-pass imaging of a fluorescent tracer was used to study the function of tumor vasculature, and tumor vascular morphology was assessed by producing vascular masks from high-resolution images. Vascular morphology was described by quantification of vascular length density, vascular area fraction, interstitial distance and vessel diameter. The function of the tumor vasculature was assessed by quantification of the blood supply times (BSTs). It was found that exposure to cyclic hypoxia resulted in higher vascular densities, a trend towards higher BST values and decreased growth rate in the tumors. The results could be associated with enhanced angiogenesis in the tumors that received the cyclic hypoxia treatment due to overexpression of pro-angiogenic genes regulated by HIF-1α.