Journal Article

Crossing the endothelial barrier during metastasis

Ridley, Anne J., d'Água, Bárbara Borda, Reymond, Nicolas

2013

Overview

Key Points To form metastases, cancer cells twice cross the endothelial cells that line blood vessels (once during intravasation and once during extravasation). Cancer cell extravasation usually occurs in small capillaries, where the cells can be physically trapped by size restriction and can then form stable attachments to endothelial cells. Many pairs of ligand–receptor molecules contribute to the process of extravasation, including selectins, integrins, cadherins, CD44 and immunoglobulin superfamily receptors. Cancer cells that are attached to endothelial cells interact with many other circulating cells in the bloodstream, including platelets, monocytes, neutrophils and natural killer cells, and these cells modulate the efficiency of cancer cell extravasation. Cytokines and chemokines that increase endothelial barrier permeability (and therefore increase the efficiency of cancer cell extravasation) are often secreted by cancer cells or by associated circulating cells. The processes of intravasation and extravasation are thought to be crucial for cancer cell dissemination and metastasis. This Review describes how cancer cells cross the endothelial barrier, with a focus on the extravasation step. During metastasis, cancer cells disseminate to other parts of the body by entering the bloodstream in a process that is called intravasation. They then extravasate at metastatic sites by attaching to endothelial cells that line blood vessels and crossing the vessel walls of tissues or organs. This Review describes how cancer cells cross the endothelial barrier during extravasation and how different receptors, signalling pathways and circulating cells such as leukocytes and platelets contribute to this process. Identification of the mechanisms that underlie cancer cell extravasation could lead to the development of new therapies to reduce metastasis.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 101/62 / 14/63 / 631/67/2328 / 631/67/322 / 631/67/327 / 631/80/84 / 64/116 / 64/60 / Animals / Basement Membrane - metabolism / Basement Membrane - pathology / Biomedicine / Cancer Research / Cell Adhesion / Cell Adhesion Molecules - metabolism / Cell membranes / Cell Shape / Chemokines - physiology / Endothelium, Vascular - pathology / Humans / Metastasis / Neoplasm Invasiveness / Neoplasms - metabolism / Neoplasms - pathology / Neoplastic Cells, Circulating - metabolism / Neoplastic Cells, Circulating - pathology / Neoplastic processes / Physiological aspects / review-article / Transendothelial and Transepithelial Migration