The selectin–selectin ligand axis in tumor progression

Abstract

This review will document that the selectin-selectin ligand axis is actively involved in tumor progression and drives this process. The involvement of selectins and their ligands in tumor progression takes place at three levels which will be reviewed: Interaction of tumor cells with platelets and leukocytes resulting in the formation of circulating emboli; interaction of tumor cells with endothelial cells leading to extravasation of the tumor cells; and utilization of reciprocal pro malignancy signals delivered by the selectins or by their ligands to interacting cells that express the corresponding co-receptor. We propose that the selectin-selectin ligand mediated interactions between cells in the tumor microenvironment constitute an axis of evil, that it be included in the list of pro malignancy factors, and that molecules associated with this axis serve as targets for cancer therapy.

Variation in Carbohydrates between Cancer and Normal Cell Membranes Revealed by Super‐Resolution Fluorescence Imaging

“…In fact, the interactions of carbohydrates with CBPs can affect tumor cell interactions with normal cells or with the extracellular matrix during metastatic spread and growth. These bindings of carbohydrate ligands and endogenous lectins not only occur in the formation of carbohydrate patterns on cell membranes (i.e., via galectins on tumor cells),21 but also in interactions of tumor cells and local microenvironment (via selectins on the endothelial surface,22 or via siglecs on macrophages23) in various metastasis processes. As known, carbohydrate‐related molecular interactions are generally weak and of low affinity, thus multivalent bindings between CBPs and carbohydrates via clustering together carbohydrates ligands of glycoconjugates are reported to be typically necessary in various cellular processes 24, 25, 26.…”

Biomarkers of endothelial dysfunction: can they help us deciphering systemic inflammation and sepsis?

“…They are the key mediators of leukocyte trafficking and hemostasis implicated in many human diseases including systemic inflammatory disorders and sepsis (Kansas 1996;Laubli and Borsig 2010;Ley 2003;McEver 1997;Witz 2008). The selective recruitment of subpopulations of circulating leukocytes to the sites of injury or inflammation is a complex process orchestrating the interaction of primary (selectin) and activation-dependent (integrin) adhesion molecules.…”

Systemic inflammation increases cancer cell adhesion to hepatic sinusoids by neutrophil mediated mechanisms

“…Interactions between endothelial selectins and tumor cell selectin ligands have been implicated in the metastatic process. [5][6][7][8] Selectins are a family of transmembrane glycoproteins possessing an extracellular lectin domain that binds to carbohydrate moieties present on their ligands. 9 The three known selectins that function as cell adhesion molecules are expressed on the surface of endothelial cells (E-selectin and P-selectin), platelets (P-selectin) and leukocytes (L-selectin).…”

“…3 The hematogenous dissemination of cancer cells from a primary tumor to distant organs involves a cascade of sequential steps (reviewed in Refs. 4,5). The adhesion of circulating tumor cells to the vascular endothelium of distant organs is a key step in the metastatic cascade that may determine the organ tropism and extent of metastasis.…”