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Critical Reviews™ in Immunology

Impact factor: 3.698

ISSN Print: 1040-8401
ISSN Online: 2162-6472

Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v30.i6.30
pages 529-545

Endothelial Cells as Key Determinants of the Tumor Microenvironment: Interaction with Tumor Cells, Extracellular Matrix and Immune Killer Cells

Salem Chouaib
INSERM, U1186, Villejuif, France; Gustave Roussy Cancer Campus, Villejuif, France; and University Paris-Saclay, Faculty of Medicine, Le Kremlin Bicetre, France
Claudine Kieda
Centre National de la Recherche Scientifique (CNRS), Centre de Biophysique Moléculaire, Orléans
Houssem Benlalam
Institut National de la Sant#233; et de la Recherche Médicale (INSERM), Villejuif, France, Institut Gustave Roussy, Villejuif
Muhammad Zaeem Noman
Institut National de la Sante et de la Recherche Medicale Unite 753, Villejuif, France, Institut Gustave Roussy, Villejuif, France
Fathia Mami-Chouaib
Institut National de la Sant#233; et de la Recherche Médicale (INSERM), Villejuif, France, Institut Gustave Roussy, Villejuif
Curzio Ruegg
Laboratory of Tumor Angiogenesis and Metastasis, Pathology Unit, Department of Medicine, Faculty of Science, University of Fribourg (UNIFR), Fribourg

ABSTRACT

Besides tumor cells, the tumor microenvironment harbors a variety of host-derived cells, such as endothelial cells, fibroblasts, innate and adaptive immune cells. It is a complex and highly dynamic environment, providing very important cues to tumor development and progression. Tumor-associated endothelial cells play a key role in this process. On the one hand, they form tumor-associated (angiogenic) vessels through sprouting from locally preexisting vessels or recruitment of bone marrow-derived endothelial progenitor cells, to provide nutritional support to the growing tumor. On the other hand, they are the interface between circulating blood cells, tumor cells and the extracellular matrix, thereby playing a central role in controlling leukocyte recruitment, tumor cell behavior and metastasis formation. Hypoxia is a critical parameter modulating the tumor microenvironment and endothelial/tumor cell interactions. Under hypoxic stress, tumor cells produce factors that promote tumor angiogenesis, tumor cell motility and metastasis. Among these factors, VEGF, a main angiogenesis modulator, can also play a critical role in the control of immune tolerance. This review discusses some aspects of the role of endothelial cells within tumor microenvironment and emphasizes their interaction with tumor cells, the extracellular matrix and with immune killer cells. We will also address the role played by circulating endothelial progenitor cells and illustrate their features and mechanism of recruitment to the tumor microenvironment and their role in tumor angiogenesis.