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Endothelial Cell-Cell Junctions in Tumor Angiogenesis

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Tumor Angiogenesis

Abstract

Angiogenesis is a complex and tightly regulated multistep process whose deregulations induce an aberrant growth of blood vessels, strongly associated with cardiovascular pathologies and also with tumor progression in most of the solid cancers. Tumor vessels are essentially smaller, disorganized, and leaky. In this scenario, the endothelial cells that mat the inner side of the vascular wall are excessively activated and exhibit higher proliferation rate and enhanced migratory phenotype. The loss of endothelial barrier integrity is one of the most striking phenotype of the tumor vasculature and contributes to exacerbate angiogenesis, tissular damage, stromal abnormalities, perivascular inflammation, and poor drug delivery.

Physiologically, the endothelial barrier controls the bidirectional passage and the flux of fluids, molecules, and cells from the blood stream to the irrigated tissues. In the tumor microenvironment, this barrier is strongly permeable, allowing thereby unrestricted, anarchic movements across the endothelium. Molecularly, the dismantlement of the endothelial cell-cell junctions, notably those formed by the cell-cell adhesion molecule VE-cadherin, supports vascular leakage in the tumor microenvironment.

There is now growing evidence that restoring the function of endothelial cell-cell junctions could help normalizing the tumor vasculature and further support the use of anti-permeability agents as potent means to interfere with tumor-driven angiogenesis.

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Acknowledgment

We would like to thank past and present members of the SOAP Team and in particular former PhD students Lucas Treps and Jagoda Hebda. Research is supported by Ligue Nationale Contre le Cancer (comité Loire-Atlantique, Maine-et-Loire, Morbihan, Vendée, FR) and Fondation ARC pour la Recherche sur le Cancer (FR). JG is laureate of Connect Talent award from Région Pays-de-La-Loire (FR) and Nantes-Métropole (FR).

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  1. CRCINA, INSERM, CNRS, Universite d’Angers, Universite de Nantes, SOAP Team, Nantes, France

    Quentin Roux

  2. CRCINA, INSERM, CNRS, Universite d’Angers, Universite de Nantes, Institut de Cancerologie de l’Ouest, SOAP Team, Nantes, France

    Julie Gavard

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  1. Quentin Roux
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  2. Julie Gavard
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Correspondence to Julie Gavard .

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  1. Tumor Biology Center, Freiburg, Baden-Württemberg, Germany

    Dieter Marmé

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Roux, Q., Gavard, J. (2018). Endothelial Cell-Cell Junctions in Tumor Angiogenesis. In: Marmé, D. (eds) Tumor Angiogenesis. Springer, Cham. https://doi.org/10.1007/978-3-319-31215-6_39-1

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