A quantitative assessment of microvessel ultrastructure in C6 astrocytoma spheroids transplanted to brain and to muscle

Abstract

Normal blood vessels invading a growing neoplasm undergo dramatic changes in morphology. Whether vessel characteristics are dictated entirely by the tumor, or from developmental restrictions in normal vessels from which tumor vessels originate is not known. To address this question we challenged two morphologically different types of capillaries (brain and muscle) with the same tumor environment (C6 astrocytoma), and quantified the invading vessel morphology. A vascular spheroids of C6 astrocytoma cells were implanted singly into rat cerebral cortex or iliacus muscle. Microvessels from the tumor, peritumoral tissue and control tissue were examined ultrastructurally and quantified. Tumor vessels differed significantly from host vessels but not from each other, regardless of implantation site. Neoplastic vessels were thick-walled relative to normal host vessels, had low densities of mitochondria and vesicular structures, and had both fenestrations and enlarged junctional clefts characteristic of highly permeable vessels. Control brain vessels were typically thin-walled, had a high density of mitochondria, a low density of endothelial vesicles and continuous tight junctions. Control muscle vessels were thin-walled with a low density of mitochondria, high density of vesicles and junctional zones with occasional enlarged clefts. Peritumoral vessel morphology was intermediate between that of tumor and the corresponding control tissue. We propose that C6 astrocytoma cells influence invading endothelial cells to develop a permeable phenotype radically different from host tissue endothelium, and host vessel phenotype does not influence tumor vessel morphology.