Vasculogenic mimicry and tumor angiogenesis

Tumors require a blood supply for growth and hematogenous dissemination. Mu ch attention has been focused on the role of angiogenesis-the recruitment o f new vessels into a tumor from pre-existing vessels. However, angiogenesis may not be the only mechanism by which tumors acquire a microcirculation. Highly aggressive and metastatic melanoma cells are capable of forming high ly patterned vascular channels ill vitro that are composed of a basement me mbrane that stains positive with the periodic acid-Schiff (PAS) reagent in the absence of endothelial cells and fibroblasts. These channels formed in vitro are identical morphologically to PAS-positive channels in histologica l preparations from highly aggressive primary uveal melanomas, in the verti cal growth phase of cutaneous melanomas, and in metastatic uveal and cutane ous melanoma. The generation of microvascular channels by genetically dereg ulated, aggressive tumor cells was termed "vasculogenic mimicry" to emphasi ze their de novo generation without participation by endothelial cells and independent of angiogenesis. Techniques designed to identify the tumor micr ocirculation by the staining of endothelial cells may not be applicable to tumors that express vasculogenic mimicry. Although it is not known if thera peutic strategies targeting endothelial cells will be effective in tumors w hose blood supply is formed by tumor cells in the absence of angiogenesis, the biomechanical and molecular events that regulate vasculogenic mimicry p rovide opportunities for the development of novel forms of tumor-targeted t reatments. The unique patterning characteristic of vasculogenic mimicry pro vides an opportunity to design noninvasive imaging techniques to detect hig hly aggressive neoplasms and their metastases.