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A. Y. Lin, L. Leach, K. Valyi-Nagy, M. Apushkin, A. J. Maniotis, J. Pe'er, R. Folberg; Validating the Tumor Cell Origins of Vasculogenic Mimicry Patterns, a Significant Prognostic Histological Factor in Uveal Melanomas. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4784.
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Multiple independent pathology groups have confirmed the prognostic significance of detecting looping vasculogenic mimicry (VM) patterns in histological sections of uveal melanomas. Although in vitro studies have demonstrated that highly invasive melanoma cells generate VM patterns, some pathologists contend that vasculogenic mimicry patterns are fibrovascular septa that originate from a host stromal response to the tumor. We have shown previously that there are morphological and immunohistochemical differences between fibrovascular septa and VM patterns. To validate our hypothesis that VM patterns are an attribute of the invasive tumor cell and not part of the host response, we studied the histogenesis of VM pattern formation in a mouse model.
OCM1a human uveal melanoma cells were injected into the liver of 15 SCID mice. Animals were sacrificed after 6-8 weeks, and tumor nodules examined histologically. Sections were stained with mouse monoclonal anti-laminin antibody specific for human laminin or rabbit polyclonal anti-laminin antibody that cross reacts with both mouse and human laminin. Three-dimensional reconstruction of VM patterns were generated by laser scanning confocal microscopy assisted by immersion visualization techniques described by us previously.
Vasculogenic mimicry patterns, identical to those demonstrated in human primary and metastatic melanoma, formed in the xenografts. The monoclonal antibody to human laminin stained VM patterns in the melanoma nodules but did not label vessels in the mouse liver or control mouse kidney. The polyclonal antibody that reacts with human and mouse laminin stained VM patterns in the melanoma nodules and labeled mouse vessels in the liver as well as basement membranes in the mouse kidney. Three dimensional reconstructions of VM patterns in the xenograft revealed an architecture identical to VM patterning in human tumors.
VM patterns in the xenograft consist of human laminin, rather than laminin coopted from the mouse host, providing another line of evidence confirming the tumor cell origin of this histologically significant marker of tumor progression and further distinguishing these patterns from host-derived fibrovascular septa.
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