ABSTRACT
Crossing the vascular endothelium is a necessary stage for circulating cells aiming to reach distant organs. Leukocyte passage through the endothelium, known as transmigration, is a multistep process during which immune cells adhere to the vascular wall, migrate and crawl along the endothelium until they reach their exit site. Similarly, circulating tumor cells (CTCs), which originate from the primary tumor or reseed from early metastatic sites, disseminate using the blood circulation and also must cross the endothelial barrier to set new colonies in distant organs. CTCs are thought to mimic arrest and extravasation utilized by leukocytes; however, their extravasation also requires processes that, from an endothelial perspective, are specific to cancer cells. Although leukocyte extravasation relies on maintaining endothelial impermeability, it appears that cancer cells can indoctrinate endothelial cells into promoting their extravasation independently of their normal functions. In this Review, we summarize the common and divergent mechanisms of endothelial responses during extravasation of leukocytes (in inflammation) and CTCs (in metastasis), and highlight how these might be leveraged in the development of anti-metastatic treatments.
Footnotes
Funding
Our work in this area is supported by the INCa (Institut National Du Cancer, French National Cancer Institute), the National Plan Cancer initiative, charities [La Ligue contre le Cancer, ARC (Association pour la Recherche sur le Cancer), FRM (Fondation pour la Recherche Médicale)], Ruban Rose, Rohan Athlétisme Saverne and Trailers de la Rose, the Region Grand Est, INSERM and the University of Strasbourg. A.D. is supported by a PhD fellowship from the French Ministry of Science (MESRI), and fellowships from La Ligue contre le Cancer and Alsace contre le Cancer.
