| First Author | Reticker-Flynn NE | Year | 2015 |
| Journal | Cancer Discov | Volume | 5 |
| Issue | 2 | Pages | 168-81 |
| PubMed ID | 25421439 | Mgi Jnum | J:221982 |
| Mgi Id | MGI:5643819 | Doi | 10.1158/2159-8290.CD-13-0760 |
| Citation | Reticker-Flynn NE, et al. (2015) Aberrant glycosylation promotes lung cancer metastasis through adhesion to galectins in the metastatic niche. Cancer Discov 5(2):168-81 |
| abstractText | 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. SIGNIFICANCE: Although clinical observations of elevated serum galectin-3 levels and altered glycosylation have been associated with malignancy, we identify novel roles for glycosyltransferases in promoting adhesion to galectins in the metastatic niche. This identification of a cytokine-leukocyte-glycosylation axis in metastasis provides mechanistic explanations for clinical associations between malignancy and aberrant glycosylation. |
