Review
Vasculogenic Mimicry and Tumor Angiogenesis

https://doi.org/10.1016/S0002-9440(10)64739-6Get rights and content

Tumors require a blood supply for growth and hematogenous dissemination. Much attention has been focused on the role of angiogenesis—the recruitment of 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 highly patterned vascular channels in vitro that are composed of a basement membrane 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 histological preparations from highly aggressive primary uveal melanomas, in the vertical growth phase of cutaneous melanomas, and in metastatic uveal and cutaneous melanoma. The generation of microvascular channels by genetically deregulated, aggressive tumor cells was termed “vasculogenic mimicry” to emphasize their de novo generation without participation by endothelial cells and independent of angiogenesis. Techniques designed to identify the tumor microcirculation by the staining of endothelial cells may not be applicable to tumors that express vasculogenic mimicry. Although it is not known if therapeutic strategies targeting endothelial cells will be effective in tumors whose blood supply is formed by tumor cells in the absence of angiogenesis, the biomechanical and molecular events that regulate vasculogenic mimicry provide opportunities for the development of novel forms of tumor-targeted treatments. The unique patterning characteristic of vasculogenic mimicry provides an opportunity to design noninvasive imaging techniques to detect highly aggressive neoplasms and their metastases.

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Supported by National Institutes of Health grants R01 EY10457 (to R.F.), R01 CA59702 (to M.J.C.H.) and R01 CA80318 (to M.J.C.H. and R.F.), by the University of Iowa Central Microscopy Research Facility, the Charles Hendrix Research Foundation and the University of Iowa Leading Woman Scientist Endowment (to M.J.C.H.), and in part by an unrestricted grant from Research to Prevent Blindness, Inc. Dr. Folberg is a Research to Prevent Blindness Senior Scientific Investigator.

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