Different Pathways of Macromolecule Extravasation from Hyperpermeable Tumor Vessels

doi:10.1006/mvre.1999.2207

Microvascular Research

Volume 59, Issue 1, January 2000, Pages 24-37

https://doi.org/10.1006/mvre.1999.2207 Get rights and content

Abstract

Tumor microvessels are hyperpermeable to plasma proteins, a consequence of tumor cell-secreted vascular permeability factor/vascular endothelial growth factor (VPF/VEGF). However, the pathways by which macromolecules extravasate from tumor vessels have been little investigated. To characterize tumor vessels more precisely and to elucidate the pathways by which macromolecules extravasated from them, we studied two well-defined, VPF/VEGF-secreting murine carcinomas, MOT and TA3/St. Whether grown in ascites or solid form, MOT tumors induced large, pericyte-poor “mother” vessels whose lining endothelium developed fenestrae that involved 1.8–5.6% of the surface. Fenestrae developed in parallel with markedly reduced endothelial cell vesiculo-vacuolar organelles (VVOs). TA3/St tumors, which secreted more VPF/VEGF than MOT tumors, elicited mother vessels with unchanged VVOs and without fenestrae. In both tumors, a plasma protein tracer, ferritin, extravasated through VVOs and in MOT tumors ferritin also extravasated through fenestrae. Endothelial gaps were not observed in either tumor. Thus, not all VPF/VEGF-secreting tumors induce fenestrated endothelium. Also, VVOs provide an internal store of membrane that can be transferred to the endothelial cell surface to provide the substantial increase in plasma membrane necessary for mother vessel formation in MOT tumors. Such transfer was apparently unnecessary in TA3/St tumors in which extensive early endothelial cell division provided the increased plasma membrane necessary for forming mother vessels.

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¹: Both authors contributed equally to this work.

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Regular ArticleDifferent Pathways of Macromolecule Extravasation from Hyperpermeable Tumor Vessels

Abstract

Microvasc. Res.

Microvasc. Res.

Am. J. Pathol.

Endothelial gaps: Time course of formation and closure in inflamed venules of rats

Am. J. Physiol.

Vascular permeability factor (vascular endothelial growth factor) gene is expressed differentially in normal tissues, macrophages, and tumors

Mol. Biol. Cell

Expression of vascular endothelial growth factor during embryonic angiogenesis and endothelial cell differentiation

Development

Vascular permeability factor/vascular endothelial growth factor: A multifunctional angiogenic cytokine

Expression of vascular permeability factor (vascular endothelial growth factor) by epidermal keratinocytes during wound healing

J. Exp. Med.

Intestinal capillaries. I. Permeability to peroxidase and ferritin

J. Cell Biol.

Procedural guide to specimen handling for the ultrastructural pathology service laboratory

J. Electron Microsc. Tech.

The vesiculo-vacuolar organelle (VVO): A distinct endothelial cell structure that provides a transcellular pathway for macromolecular extravasation

J. Leukocyte Biol.

Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis

Am. J. Pathol.

Regulation of extravascular coagulation by microvascular permeability

Science

Vesiculo-vacuolar organelles and the regulation of venule permeability to macromolceules by vascular permeability factor, histamine, and serotonin

J. Exp. Med.

Reinterpretation of endothelial cell gaps induced by vasoactive mediators in guinea-pig, mouse and rat: Many are transcellular pores

J. Physiol. (London)

Pathways of macromolecular extravasation across microvascular endothelium in response to VPF/VEGF and other vasoactive mediators

Microcirculation

Vascular endothelial growth factor. The trigger for neovascularization in the eye [editorial; comment]

Lab. Invest.

Tumor-derived expression of vascular endothelial growth factor is a critical factor in tumor expansion and vascular function [In Process Citation]

Cancer Res.

Location of focal silver staining at endothelial gaps in inflamed venules examined by scanning electron microscopy

Am. J. Physiol.

Regular Article
Different Pathways of Macromolecule Extravasation from Hyperpermeable Tumor Vessels