FIGURE 1.

Selectins dependent cell adhesion in normal condition and cancer progression. Endothelial activation is triggered through endogenous and exogenous stimuli from inflamed tissue. (A) Leukocyte adhesion cascade could be classified into three steps: rolling; capture, activation and arrest; which is mediated by selectins, chemokines and integrins respectively, progressing to transcellular migration. (B) Selectin-triggered endothelial activation leads to leukocyte-assisted tumor cell extravasation. Cytokines produced by the tumor cells lead to endothelial activation and leaky vasculature, resulting in leukocyte recruitment and their extravasation. (C) Tumor cell adhesion is promoted by platelets binding to endothelium and tumor cells. (D) Intracellular NFκB signalling initiated by selectin binding leading to inflammation through activation of MAPK, SRC pathways leading to activation of integrins and secretion of cytokines like CCL2, IL-8 and TNF-α. Key molecules involved in each step is shown in boxes; PSGL1: P-selectin glycoprotein ligand 1; ICAM 1 and 2: Intercellular adhesion molecule 1 and 2; VCAM 1: Vascular cell adhesion molecule 1; PECAM 1: Platelet/endothelial cell adhesion molecule 1; JAM: junctional adhesion molecule; ESAM: endothelial cell-selective adhesion molecule; ROS: Reactive oxygen species; LPS: lipopolysaccharide; TNFα: tumor necrosis factor-α; CXCL: Chemokine (C-X-C motif) ligand.