Microvessel Organization and Structure in Experimental Brain Tumors: Microvessel Populations with Distinctive Structural and Functional Properties

doi:10.1006/mvre.1999.2188

Microvascular Research

Volume 58, Issue 3, November 1999, Pages 312-328

https://doi.org/10.1006/mvre.1999.2188 Get rights and content

Abstract

We studied microvessel organization in five brain tumor models (ENU, MSV, RG-2, S635cl15, and D-54MG) and normal brain, including microvessel diameter (LMVD), intermicrovessel distance (IMVD), microvessel density (MVD), surface area (S_v), and orientation. LMVD and IMVD were larger and MVD was lower in tumors than normal brain. S_v in tumors overlapped normal brain values and orientation was random in both tumors and brain. ENU and RG-2 tumors and brain were studied by electron microscopy. Tumor microvessel wall was thicker than that of brain. ENU and normal brain microvessels were continuous and nonfenestrated. RG-2 microvessels contained fenestrations and endothelial gaps; the latter had a maximum major axis of 3.0 μm. Based on anatomic measurements, the pore area of RG-2 tumors was estimated at 7.4 × 10⁻⁶ cm² g⁻¹ from fenestrations and 3.5 × 10⁻⁵ cm² g⁻¹ from endothelial gaps. Increased permeability of RG-2 microvessels to macromolecules is most likely attributable to endothelial gaps. Three microvessel populations may occur in brain tumors: (1) continuous nonfenestrated, (2) continuous fenestrated, and (3) discontinuous (with or without fenestrations). The first group may be unique to brain tumors; the latter two are similar to microvessels found in systemic tumors. Since structure–function properties of brain tumor microvessels will affect drug delivery, studies of microvessel function should be incorporated into clinical trials of brain tumor therapy, especially those using macromolecules.

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¹: Present address: Department of Neurosurgery, National Institutes of Health, Bethesda, MD 20892.

²: Present address: Hungarian–Japanese EM Center, University Medical School of Debrecen, P.O. Box 23, H-4014 Debrecen, Hungary.

³: To whom correspondence and reprint requests should be addressed at Division of Neurology, Evanston Hospital, 2650 Ridge Avenue, Evanston, IL 60201. Fax: 847/570-1934. E-mail: [email protected].

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Regular ArticleMicrovessel Organization and Structure in Experimental Brain Tumors: Microvessel Populations with Distinctive Structural and Functional Properties

Abstract

J. Neuropathol. Exp. Neurol.

Pharmacol. Therapeut.

Microvasc. Res.

Microvasc. Res.

J. Ultrastruct. Res.

Neurol. Clin.

Cancer Treat. Rev.

J. Neurol. Sci.

Microvasc. Res.

Hum. Pathol.

Microvasc. Res.

The RG2 rat glioma model

J. Neurooncol.

Microvessel density in brain tumors

Anticancer Res.

Migration and proliferation of endothelial cells in preformed and newly formed blood vessels during tumor angiogenesis

Microvasc. Res.

Tumor angiogenesis as a prognostic assay for invasive ductal breast carcinoma

J. Natl. Cancer Inst.

Differential permeability and quantitative MR imaging of a human lung carcinoma brain xenograft in the nude rat

Am. J. Pathol.

Rat brain tumor models in experimental neuro-oncology: The 9l, C6, T9, F98, RG-2 (D74), RT-2 and CNS1 gliomas

J. Neurooncol.

Endothelial fenestral diaphragms: A quick-freeze, deep-etch study

J. Cell Biol.

Monoclonal antibody 81C6 distribution, permeability and cellular proliferation in human glioma brain xenografts: a triple label autoradiographic study

Proc. Am. Assoc. Cancer Res.

Heterogeneity of genotypic and phenotypic characteristics of fifteen permanent cell lines derived from human gliomas

J. Neuropathol. Exp. Neurol.

Chemotherapy of brain tumors: Physiological and pharmacokinetic considerations

Semin. Oncol.

Regional blood flow in ethylnitrosourea (ENU)-induced brain tumors

Ann. Neurol.

Regional blood-to-tissue transport in ethylnitrosourea (ENU)-induced brain tumors

Ann. Neurol.

Regional localization of a glioma associated antigen defined by monoclonal antibody 81C6: Implications for diagnosis and therapy

Cancer Res.

The transport of alpha-aminoisobutyric acid across brain capillary and cellular membranes

J. Cereb. Blood Flow Metab.

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

J. Neuropathol. Exp. Neurol.

The permeability of capillaries in various organs as determined by the use of the “indicator diffusion” method

Acta Physiol. Scand.

Quantitation and physiological characterization of angiogenic vessels in mice: Effect of basic fibroblast growth factor, vascular endothelial growth factor/vascular permeability factor, and host microenvironment

Am. J. Pathol.

Do anticancer agents reach the tumor target in the human brain

Canc. Chemother. Pharmacol.

Structural, ultrastructural, and functional correlations among local capillary systems with the brain

Practical Methods in Electron Microscopy

Permeability of different brain tumor models to horseradish peroxidase

J. Neuropathol. Exp. Neurol.

Regional measurements of blood-to-tissue transport in transplanted RG-2 rat gliomas

Cancer Res.

Regional blood flow and blood-to-tissue transport in five brain tumor models: Implications for chemotherapy

Regional measurements of blood flow in transplanted RG-2 rat gliomas

Cancer Res.

Quantitative measurements of capillary transport in human brain tumors by computed tomography

Ann. Neurol.

Topography of capillary density, glucose metabolism, and microvascular function within the rat inferior colliculus

J. Cereb. Blood Flow Metab.

Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment

Proc. Natl. Acad. Sci. USA

Transport of molecules across tumor vasculature

Canc. Metas. Rev.

Vascular and interstitial barriers to delivery of therapeutic agents in tumors

Canc. Metas. Rev.

Barriers to drug delivery in solid tumors

Sci. Am.

Delivery of molecular medicine to solid tumors

Science

The next frontier of molecular medicine: Delivery of therapeutics

Nat. Med.

Regular Article
Microvessel Organization and Structure in Experimental Brain Tumors: Microvessel Populations with Distinctive Structural and Functional Properties