Purpose: Recently, it was reported that tumor cells themselves generate channels and networks in three-dimensional culture and can be found lining channels (some containing red blood cells [RBCs]) in vivo, and they express endothelial or vascular genes in aggressive uveal melanoma. The implications of these data for current insights in the involvement of angiogenesis in tumor growth, metastasis and therapeutic intervention are considerable. Therefore, this possibility was investigated in the current study.

Methods: Thirty human uveal melanomas and 20 xenografts of human cutaneous melanoma were analyzed by Azan histochemistry and immunostaining of endothelial markers. Additionally, in xenografted tumors a tracer study was performed with confocal microscopy and immunoelectron microscopy.

Results: Lumina or spaces without endothelial lining containing RBCs were not detected in any lesion. Functional evaluation of the vasculature in xenografts demonstrated rapid tracer appearance both inside and outside blood vessels. Outside blood vessels it spread along matrix networks of arcs and back-to-back loops. Confocal microscopy showed that this extracellular matrix was deposited as stromal sheets around nests of tumor cells. Laminin immunostaining revealed that between sheets surrounding adjacent nests, spaces were present. These spaces were filled, however, with collagen and different types of cells, including cells stained for macrophage markers.

Conclusions: Although no evident endothelium-free and RBC-containing channels were present in the tissues examined, there are fluid-conducting spaces in the form of stromal sheets between nests of tumor cells. In this stromal network, blood vessels are embedded. The authors postulate that this extracellular matrix tissue represents a fluid-conducting meshwork.