The involvement of apoptosis in melanoma vasculogenic mimicry

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During development, the formation and remodeling of the primary vascular network occurs by vasculogenesis and angiogenesis. In 1999, the concept of vasculogenic mimicry was introduced to describe the unique ability of highly aggressive tumor cells to form a capillary-like structure and a matrix-rich patterned network in three-dimensional culture that mimic the embryonic vasculogenic network. In this study, we examined the ability of melanoma cells derived from patients with disseminated melanoma to engage in vasculogenic mimicry in order to identify key parameters in the complexity of the formation of capillary-like structure. We showed that disseminated melanoma as well as uveal and cutaneous melanoma adopts a vascular-related phenotype and engages in vasculogenic mimicry: the main geometrical features of capillary-like structure are determined during the first step of the vascular network assembly. We provided experimental evidence that capillary-like structure formation requires apoptotic cell death through activation of a caspase-dependent mechanism: a broad range caspase inhibitor zVAD-fmk and a caspase-3 inhibitor DEVD blocked capillary-like structure formation. Apoptosis occurs before capillary-like structure formation but not after capillary-like structures have assembled. These observations may provide a better understanding of the mechanisms involved in melanoma vasculogenic mimicry.