Publication Type:Journal Article
Source:Cancer Discov, Volume 5, Issue 2, p.168-81 (2015)
Metastasis is the leading cause of cancer-associated deaths. Although 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 the establishment of a protumorigenic 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-6C(hi) leukocytes. Tumors mobilize these myeloid populations through secretion of soluble factors, including IL6. 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 St6GalNAc4 glycosyltransferase activity that inhibits further glycosylation of this carbohydrate motif and promotes metastasis.