[Vasculogenic mimicry--potential target for tumor therapy]

Abstract

In 1999, Maniotis described a novel process by which tumors develop a highly patterned microcirculation that was independent of angiogenesis: in aggressive primary and metastatic melanomas, tumor cells generate non-endothelial cell-lined microcirculatory channels composed of extracellular matrix and lined externally by tumor cells. They named the process "vasculogenic mimicry" (VM). Folberg used PAS staining to show VM network, and identified 7 morphologic patterns of PAS-positive channels uveal melanomas which were confirmed as tubular type and patterned matrix type. Maniotis suggested PAS-positive patterns of VM in uveal melanoma are indeed a form of tumor microcirculation which is different from angiogenesis, and it is not a stromal host response at the interface between the tumor and the surrounding host stroma. VM has also been observed in carcinomas of the breast, prostate, ovary and lung, glioblastoma, synoviosarcoma, rhabdomyosarcoma, and phaeochromocytoma, and in the process of placenta formation from cytotrophoblasts. The molecular "signature" of aggressive melanoma cells is illustrative of an undifferentiated cell with a gene expression profile that is similar to that of embryonic-like cells. VE-cadherin, EphA2, laminin5 gamma2, matrix metalloproteinases (MMPs), vascular endothelial growth factor-C (VEGF-C), LYVE1, TF and NOTCH are important components of molecular switch of vasculogenic mimicry. The heterogeneity of tumor vasculature and the molecular regulation mechanisms present an opportunity for tumor therapy.