Journal
MICROVASCULAR RESEARCH
Volume 59, Issue 1, Pages 24-37Publisher
ACADEMIC PRESS INC
DOI: 10.1006/mvre.1999.2207
Keywords
ascites tumors; solid tumors; angiogenesis; vascular permeability factor/vascular endothelial growth factor (VPF/VEGF); vesiculo-vacuolar organelle (VVO); electron microscopy; endothelium; permeability
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Funding
- NATIONAL CANCER INSTITUTE [R01CA050453] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI033372] Funding Source: NIH RePORTER
- NCI NIH HHS [CA50453] Funding Source: Medline
- NIAID NIH HHS [AI33372] Funding Source: Medline
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Tumor microvessels are hyperpermeable to plasma proteins, a consequence of turner cell-secreted vascular permeability factor/vascular endothelial growth factor (VPF/VEGF). However, the pathways by which macromolecules extravasate from tumor vessels hare 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. (C) 2000 Academic Press.
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