FRACTAL CHARACTERISTICS OF TUMOR VASCULAR ARCHITECTURE DURING TUMOR-GROWTH AND REGRESSION

Objective: Tumor vascular networks are different from normal vascular networks: but the mechanisms underlying these differences are not know n. Understanding these mechanisms may be the key to improving the effi cacy of treatment of solid tumors. Methods: We studied the fractal cha racteristics of two-dimensional normal and tumor vascular networks gro wn in a murine dol sal chamber preparation and imaged with an intravit al microscopy station. Results: During tumor growth and regression, th e vasculature in the tumor has scaling characteristics that reflect th e changing state of the tissue. Growing turners show vascular networks that progressively deviate from their normal pattern, in which they s eem to follow diffusion-limited. aggregation tu a pathological conditi on 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 substra te properties rather than gradients of a diffusing substance, such as an angiogenic growth factor. During tumor regression, the fractal char acteristics 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. Con clusions: In the present contest, tile percolation-like nature of tumo r vasculature implies that tumor vascular networks possess inherent ar chitectural obstacles to the delivery of diffusible substances such as oxygen and drugs.