Aberrant Glycosylation Promotes Lung Cancer Metastasis through Adhesion to Galectins in the Metastatic Niche
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...
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| Other Authors: | , , , |
| Format: | Article |
| Language: | English |
| Published: |
American Association for Cancer Research,
2015-11-10T13:47:44Z.
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| Subjects: | |
| Online Access: | Get fulltext |
| Summary: | 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[superscript +]Gr-1[superscript + ]and CD11b[superscript +]Ly-6C[superscript 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. National Cancer Institute (U.S.) (Koch Institute Support (Core) Grant P30-CA14051) Ludwig Center for Molecular Oncology (Graduate Fellowship) Stand Up To Cancer (Translational Research Grant SU2C-AACR-DT0309) Howard Hughes Medical Institute David H. Koch Institute for Integrative Cancer Research at MIT (CTC Project) |
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