A Quantitative Assessment of Microvessel Ultrastructure in C₆Astrocytoma 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.

Barrier properties of testis microvessels.

“…The expanded clefts that we observed in testis capillaries are infrequent and have the right dimensions to represent such breaks. Since we never observed such expanded clefts in normal adult brain where permeability is low but have found them in developing brain (47), muscle (48), and brain tumors (49) where permeability is increased, we suggest that they represent channels through the junctions and that they account for the higher permeability of testis microvessels.…”

Histological Examination of False Positive Tissue Resection Using 5-Aminolevulinic Acid-Induced Fluorescence Guidance

“…17) However, 5-ALA is taken up in brain tumor cells, forming excess PPIX, because of the damaged BBB in brain tumor. 2) The PPIX density also leaks into the edematous tissue surrounding the tumor through the damaged BBB. 13,19) Exposure to an appropriate wavelength of light causes PPIX to fluoresce, 8) allowing intraoperative diagnosis of neoplastic cells by visual differentiation from surrounding normal cells.…”

Mechanisms of Tumor-Associated Edema: A Review

“…12 These results suggest that irrespective of the host tissue microvessels in which they are grown, C6 astrocytoma tumor cells organize the development and the final morphological features of the microvessels which vascularize them. Specific endothelial cell morphological changes are seen in tumor vessel profiles from the C6 astrocytoma spheroid implantation model.…”

“…In this communication, an attempt will be made to evaluate the role of each of these suggested mechanisms in the murine C6 spheroid implantation model 12 and human cerebral tumors with an emphasis on the possible role of inflammatory processes and the influence of non-steroidal anti-inflammatory drugs (NSAID's).…”