gms | German Medical Science

Objective: The blood vessels are the bodies' highways delivering nutrients and satisfying all the needs of the tissues and organs of the human body. The process of angiogenesis is highly connected with the development of organs and tissues itself. Further, during tissue maintenance and regeneration supply of oxygen and nutrients for cell function and survival is required. In particular proliferating cells within a tissue depend strongly on continuous blood supply and thus create a microenvironment which encourages the generation and growth of blood vessels. In the past, a variety of assays has been established to study angiogenesis, but very few allow investigations in a model with organotypic cellular and microenvironmental composition.

Methods: Previously, we established an “Organotypic Glioma Invasion Model” (OGIM) which allows to monitor in real-time tumor invasion, metastasis and angiogenesis in an in-vitro experiment with in-vivo conditions. Therefore, we extended this ex-vivo system by tracking the distribution of genetically marked glioma cells (RFP, GFP) and vascular components.

Results: In this model, we found that the blood-vessel architecture is altered drastically in and around the tumor-bulk in comparison to normal brain tissue without tumor contact. Within the tumor, the blood vessels show ranging diameters with erratic alterations of vessel types and course. The peritumoral region is characterized by the absence of large diameter vessels, or metarterioles whereas unaffected brain regions display an even and regular distribution of vessels from capillaries, arterioles and metarterioles. We classified these alterations in physiological vessel architecture with large diameter vessels at the pial surface and smaller vessels radiating into the cortex. In contrast, vessels in the peritumoral area show a heterogeneous and diffuse architecture. Vessels in the tumor core range from "bigger than normal" to "capillary size" diameter and represent an altered architecture in terms of variations, diameter and distribution.

Conclusions: Thus, our novel model system represents a versatile system to study tumor – brain – blood vessel interaction and thus represents a bridging assay for purely cell based in-vitro assays and in-vivo animal experiments.