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Martina C Herwig, Marta M Kilian, Frank G Holz, Daniela Wenzel, Karin U Loeffler; Origin of Tumor-Associated Vessels and Vasculogenic Mimicry in an Intraocular Murine Melanoma Model. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5066.
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© ARVO (1962-2015); The Authors (2016-present)
To study the origin of tumor-associated vessels and vasculogenic mimicry, which is associated with prognosis in human uveal melanoma, in an intraocular murine melanoma model.
Six Bac-Flt1-GFP mice (with vascular endothelium specifically labeled by eGFP) with a C57Bl/6 background received an intraocular injection of HCmel12 cells (which represent a skin melanoma cell line) in order to induce melanoma growth. The eyes were removed 10 days after tumor cell injection and the vascular pattern of the murine vessels were investigated with a Zeiss Axio Zoom microscope. Following our standardized imaging protocol, the eyes were immediately fixed in 4% paraformaldehyde and embedded in paraffin or submitted for cryoconservation. Immunohistochemical stains for von Willebrand factor (vWf), vascular endothelial cadherin (VEC) which is supposed to stain vasculogenic mimicry and vascular endothelial cell adhesions, and Green Fluorescent Protein (GFP) as well as immunofluorescent stains for vWf and VEC were performed to characterize and distinguish between host-derived (GFP-expressing) vessels and tumor-derived vessels.
In this model, tumor growth could be induced in all experimental eyes. Macroscopic imaging showed a network of GFP-labelled vessels on the tumor surface. Histologic tumor characteristics comprised tumor cell pleomorphism, infiltration by inflammatory cells, cooption of blood vessels, and vasculogenic mimicry. Analysis of the immunohistochemical/immunofluorescence stains revealed an expression of GFP in all blood vessels including tumor vessels. Vasculogenic mimicry was neither labelled by GFP nor vWf. However, extracellular structures were partially stained with VEC.
This preliminary study used a novel mouse model for intraocular melanoma which allows for discrimination between host- and tumor-derived vascular structures. The findings indicate that true intratumoral vessels had apparently a host-derived origin while vasculogenic mimicry structures were not derived from host vessels and are probably tumor-derived. Further studies in this model are needed to address potential factors for tumor vasculature and microcirculation and to further analyze the origin of vasculogenic mimicry.
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