Aberrant glycosylation promotes lung cancer metastasis through adhesion to galectins in the metastatic niche

Menée à l'aide de modèles murins d'adénocarcinome du poumon, cette étude met en évidence des mécanismes par lesquels une glycoprotéine, la galectine-3, favorise le développement d'une niche métastatique

Résumé en anglais

Metastasis is the leading cause of cancer-associated deaths. While dissemination of tumor cells likely occurs early in tumorigenesis, the constituents of the microenvironment play essential rate-limiting roles in determining whether these cells will form clinically-relevant tumors. Recent studies have uncovered many molecular factors that contribute to establishment of a pro-tumorigenic metastatic niche. Here, we demonstrate that galectin-3, whose expression has clinical associations with advanced malignancy and poor outcome, contributes to metastatic niche formation by binding to carbohydrates on metastatic cells. We show that galectin-3 is expressed early during tumorigenesis by both CD11b+Gr-1+ and CD11b+Ly-6Chi leukocytes. Tumors mobilize these myeloid populations through secretion of soluble factors including IL-6. We find that metastatic cancer cells exhibit elevated presentation of the oncofetal galectin-3 carbohydrate ligand, the Thomsen-Friedenreich Antigen, on their surfaces as a result of altered C2GnT2 and St6GalNAcIV glycosyltransferase activity that inhibits further glycosylation of this carbohydrate motif and promotes metastasis.