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Reference: Carbonell, WS, Ansorge, O, Sibson, N et al., (2009). The vascular basement membrane as "soil" in brain metastasis. PloS one, 4 (6), e5857.Citable link to this page:


The vascular basement membrane as "soil" in brain metastasis.

Abstract: Brain-specific homing and direct interactions with the neural substance are prominent hypotheses for brain metastasis formation and a modern manifestation of Paget's seed and soil concept. However, there is little direct evidence for this neurotropic growth in vivo. In contrast, many experimental studies have anecdotally noted the propensity of metastatic cells to grow along the exterior of pre-existing vessels of the CNS, a process termed vascular cooption. These observations suggest the soil for malignant cells in the CNS may well be vascular, rather than neuronal. We used in vivo experimental models of brain metastasis and analysis of human clinical specimens to test this hypothesis. Indeed, over 95% of early micrometastases examined demonstrated vascular cooption with little evidence for isolated neurotropic growth. This vessel interaction was adhesive in nature implicating the vascular basement membrane (VBM) as the active substrate for tumor cell growth in the brain. Accordingly, VBM promoted adhesion and invasion of malignant cells and was sufficient for tumor growth prior to any evidence of angiogenesis. Blockade or loss of the beta1 integrin subunit in tumor cells prevented adhesion to VBM and attenuated metastasis establishment and growth in vivo. Our data establishes a new understanding of CNS metastasis formation and identifies the neurovasculature as the critical partner for such growth. Further, we have elucidated the mechanism of vascular cooption for the first time. These findings may help inform the design of effective molecular therapies for patients with fatal CNS malignancies.

Peer Review status:Peer reviewedPublication status:PublishedVersion:Publisher's version Funder: Cancer Research UK   Funder: United States Department of Defense   Funder: National Institutes of Health   Funder: Medical Research Council   Notes:Copyright 2009 Carbonell et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Bibliographic Details

Publisher: Public Library of Science

Publisher Website:

Journal: PloS onesee more from them

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Issue Date: 2009

pages:Article: e5857


Urn: uuid:98fb0784-6c91-4d59-9a28-70de96f8cc32

Source identifier: 223355

Eissn: 1932-6203


Issn: 1932-6203 Item Description

Type: Journal article;

Language: eng

Version: Publisher's versionKeywords: Animals Mice, Inbred BALB C Humans Mice Basement Membrane Brain Brain Neoplasms Neoplasm Metastasis Neoplasm Transplantation Cell Proliferation Cell Line, Tumor Central Nervous System Neoplasms Neoplasm Invasiveness Neovascularization, Pathologic Antigens, CD29 Tiny URL: pubs:223355


Autor: Carbonell, WS - institutionUniversity of Oxford - - - Ansorge, O - institutionUniversity of Oxford Oxford, MSD, Clinical Neurosci



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