Figure 1. Selectin-dependent signaling during cancer progression.

A) Primary tumor sites: Tumor cells produce various cytokines leading to endothelial activation that result in a leaky vasculature. Tumor-derived chemokines facilitate leukocyte recruitment and their extravasation. Leukocytes expressing PSGL-1 infiltrate tumors through binding to vascular selectins (P- and E-selectin). Platelets further promote leukocyte adhesion through P-selectin-mediated interactions. B) Metastatic sites: Selectins promote tumor cell-endothelial interaction and the recruitment of leukocytes. a: Platelet binding to tumor cells and to the endothelium promote tumor cell adhesion; b: Platelet-tumor cell interactions are largely facilitated by P-selectin; c: Selectin-triggered endothelial activation leads to leukocyte-assisted tumor cell extravasation. C) The intracellular signaling in leukocytes is initiated through selectin-binding to PSGL-1 on leukocytes resulting in 1: activation of MAPK and src kinase pathways; 2: activation of integrins; 3: activation of NF-κB pathways and secretion of cytokines (e.g. CCL2, IL-8 or TNF-α; 4: shedding of cell surface L-selectin.