Fractal characteristics of tumor vascular architecture during tumor growth and regression

Abstract

Objective: Tumor vascular networks are different from normal vascular networks, but the mechanisms underlying these differences are not known. Understanding these mechanisms may be the key to improving the efficacy of treatment of solid tumors.

Methods: We studied the fractal characteristics of two-dimensional normal and tumor vascular networks grown in a murine dorsal chamber preparation and imaged with an intravital microscopy station.

Results: During tumor growth and regression, the vasculature in the tumor has scaling characteristics that reflect the changing state of the tissue. Growing tumors show vascular networks that progressively deviate from their normal pattern, in which they seem to follow diffusion-limited aggregation to a pathological condition in which they display scaling similar to percolation clusters near the percolation threshold. The percolation-like scaling indicates that the key determinants of tumor vascular architecture are local substrate properties rather than gradients of a diffusing substance such as an angiogenic growth factor. During tumor regression the fractal characteristics of the vasculature return to an intermediate between those of growing tumors and those of healthy tissues. Previous studies have shown that percolation-like scaling generally inhibits transport.

Conclusions: In the present context, the percolation-like nature of tumor vasculature implies that tumor vascular networks possess inherent architectural obstacles to the delivery of diffusible substances such as oxygen and drugs.