Abstract
Malignant transformation of cells is associated with aberrant glycosylation presented on the cell-surface. Commonly observed changes in glycan structures during malignancy encompass aberrant expression and glycosylation of mucins; abnormal branching of N-glycans; and increased presence of sialic acid on proteins and glycolipids. Accumulating evidence supports the notion that the presence of certain glycan structures correlates with cancer progression by affecting tumor-cell invasiveness, ability to disseminate through the blood circulation and to metastasize in distant organs. During metastasis tumor-cell-derived glycans enable binding to cells in their microenvironment including endothelium and blood constituents through glycan-binding receptors – lectins. In this review, we will discuss current concepts how tumor-cell-derived glycans contribute to metastasis with the focus on three types of lectins: siglecs, galectins, and selectins. Siglecs are present on virtually all hematopoietic cells and usually negatively regulate immune responses. Galectins are mostly expressed by tumor cells and support tumor-cell survival. Selectins are vascular adhesion receptors that promote tumor-cell dissemination. All lectins facilitate interactions within the tumor microenvironment and thereby promote cancer progression. The identification of mechanisms how tumor glycans contribute to metastasis may help to improve diagnosis, prognosis, and aid to develop clinical strategies to prevent metastasis.
Highlights
The majority of cancer deaths are attributed to the metastatic spread of cancer cells to vital organs rather than to the primary tumor outgrowth
This review addresses the role of cancer-associated glycans during metastasis with the focus on endogenous lectin interactions within the tumor microenvironment
Siglec-9 binding to MUC1 expressing tumor cells was shown to induce recruitment of β-catenin in tumor cells resulting in promotion of cell growth in vitro [111]. These findings suggest that Siglec-9 engagement of carcinoma mucin MUC1 may be involved in tumor growth, ; the nature of Siglec-9 ligands as well as the cellular context in vivo remains to be defined
Summary
Malignant transformation of cells is associated with aberrant glycosylation presented on the cell-surface. Observed changes in glycan structures during malignancy encompass aberrant expression and glycosylation of mucins; abnormal branching of N-glycans; and increased presence of sialic acid on proteins and glycolipids. Accumulating evidence supports the notion that the presence of certain glycan structures correlates with cancer progression by affecting tumor-cell invasiveness, ability to disseminate through the blood circulation and to metastasize in distant organs. During metastasis tumor-cell-derived glycans enable binding to cells in their microenvironment including endothelium and blood constituents through glycan-binding receptors – lectins. We will discuss current concepts how tumor-cell-derived glycans contribute to metastasis with the focus on three types of lectins: siglecs, galectins, and selectins. Selectins are vascular adhesion receptors that promote tumor-cell dissemination.
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