Cancer cells remodel themselves and vasculature to overcome the endothelial barrier

Abstract

Metastasis refers to the spread of cancer cells from a primary tumor to distant organs mostly via the bloodstream. During the metastatic process, cancer cells invade blood vessels to enter circulation, and later exit the vasculature at a distant site. Endothelial cells that line blood vessels normally serve as a barrier to the movement of cells into or out of the blood. It is thus critical to understand how metastatic cancer cells overcome the endothelial barrier. Epithelial cancer cells acquire increased motility and invasiveness through epithelial-to-mesenchymal transition (EMT), which enables them to move toward vasculature. Cancer cells also express a variety of adhesion molecules that allow them to attach to vascular endothelium. Finally, cancer cells secrete or induce growth factors and cytokines to actively prompt vascular hyperpermeability that compromises endothelial barrier function and facilitates transmigration of cancer cells through the vascular wall. Elucidation of the mechanisms underlying metastatic dissemination may help develop new anti-metastasis therapeutics.

N-cadherin in cancer metastasis, its emerging role in haematological malignancies and potential as a therapeutic target in cancer

“…Trans-endothelial migration is an important process in the haematogenous dissemination of cancer cells to distant sites [ 132 ]. Notably, studies suggest that N-cadherin promotes the trans-endothelial migration of cancer cells.…”

Phytotherapeutics in cancer invasion and metastasis

“…In this pathway, the moving tumor cells can enter to a series of lymph nodes called sentinel lymph nodes, which are often the first sites of metastasis observed for a number of cancers (Chiang, Cabrera, & Segall, ; Dua, Gui, & Isacke, ; Konstantopoulos & Thomas, ). Epithelial cancer cells, after EMT and expression of a variety of adhesion molecules to attach to vascular endothelium, secrete or induce growth factors and cytokines to increase vascular permeability that can help break endothelial barrier and facilitate transmigration of cancer cells across the vascular wall (Shenoy & Lu, ). Transforming growth factor‐β (TGF‐β) or vascular endothelial growth factor (VEGF) are two factors that can reduce endothelial barrier function, increasing the number of cancer cells entering into bloodstream.…”

Vascularized Biomaterials to Study Cancer Metastasis

“…After cancer cells intravasate, they are exposed to a multitude of stressors, including loss of cell–cell and cell–matrix adhesion, shear stresses, and attacks by the immune system. Nevertheless, some cancer cells manage to survive this tortuous trip and eventually exit the vasculature to a secondary site, a process termed extravasation . As the vasculature is involved in several key steps of metastasis, it will be the focus of this review ( Figure ).…”