Sweets for a bitter end: lung cancer cell-surface protein glycosylation mediates metastatic colonization

Abstract

Glycosylation is one of the most predominant forms of cell-surface protein modifications, yet its deregulation in cancer and contribution to tumor microenvironment interactions remain poorly understood. In this issue of Cancer Discovery, Reticker-Flynn and Bhatia characterize an enzymatic switch in lung cancer cells that triggers aberrant surface protein glycosylation patterns, adhesion to lectins on the surface of inflammatory cells, and subsequent metastatic colonization of the liver.

Figure 1

Changes in sialyl glycosylation on the surface of lung adenocarcinoma cells regulates their interaction with inflammatory monocytes. A subpopulation of tumor cells differentially express specific glycosyltransferases to truncate cell surface glycans. Gal-3 expressed at the surface of monocytes preferentially binds to truncated glycans. The Gal-3 mediated interaction between monocytes and tumor cells is observed during liver colonization, but may also occur at different steps of cancer progression to support lung tumor expansion, intravasation, survival in circulation, extravasation, and secondary outgrowth. Analogous glycoprotein modifications may be required for lung cancer metastasis to other relevant organs, such as the brain.