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...
| Main Authors: | , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
American Association for Cancer Research
2015
|
| Online Access: | http://hdl.handle.net/1721.1/99872 https://orcid.org/0000-0002-1293-2097 |
| _version_ | 1826193077763571712 |
|---|---|
| author | Reticker-Flynn, Nathan E. Bhatia, Sangeeta N |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Reticker-Flynn, Nathan E. Bhatia, Sangeeta N |
| author_sort | Reticker-Flynn, Nathan E. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T09:33:24Z |
| format | Article |
| id | mit-1721.1/99872 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:33:24Z |
| publishDate | 2015 |
| publisher | American Association for Cancer Research |
| record_format | dspace |
| spelling | mit-1721.1/998722022-09-30T15:15:28Z Aberrant Glycosylation Promotes Lung Cancer Metastasis through Adhesion to Galectins in the Metastatic Niche Reticker-Flynn, Nathan E. Bhatia, Sangeeta N Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Koch Institute for Integrative Cancer Research at MIT Reticker-Flynn, Nathan E. Bhatia, Sangeeta N. 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) 2015-11-10T13:47:44Z 2015-11-10T13:47:44Z 2014-11 2014-11 Article http://purl.org/eprint/type/JournalArticle 2159-8274 2159-8290 http://hdl.handle.net/1721.1/99872 Reticker-Flynn, N. E., and S. N. Bhatia. “Aberrant Glycosylation Promotes Lung Cancer Metastasis through Adhesion to Galectins in the Metastatic Niche.” Cancer Discovery 5, no. 2 (November 24, 2014): 168–181. https://orcid.org/0000-0002-1293-2097 en_US http://dx.doi.org/10.1158/2159-8290.cd-13-0760 Cancer Discovery Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Association for Cancer Research PMC |
| spellingShingle | Reticker-Flynn, Nathan E. Bhatia, Sangeeta N Aberrant Glycosylation Promotes Lung Cancer Metastasis through Adhesion to Galectins in the Metastatic Niche |
| title | Aberrant Glycosylation Promotes Lung Cancer Metastasis through Adhesion to Galectins in the Metastatic Niche |
| title_full | Aberrant Glycosylation Promotes Lung Cancer Metastasis through Adhesion to Galectins in the Metastatic Niche |
| title_fullStr | Aberrant Glycosylation Promotes Lung Cancer Metastasis through Adhesion to Galectins in the Metastatic Niche |
| title_full_unstemmed | Aberrant Glycosylation Promotes Lung Cancer Metastasis through Adhesion to Galectins in the Metastatic Niche |
| title_short | Aberrant Glycosylation Promotes Lung Cancer Metastasis through Adhesion to Galectins in the Metastatic Niche |
| title_sort | aberrant glycosylation promotes lung cancer metastasis through adhesion to galectins in the metastatic niche |
| url | http://hdl.handle.net/1721.1/99872 https://orcid.org/0000-0002-1293-2097 |
| work_keys_str_mv | AT retickerflynnnathane aberrantglycosylationpromoteslungcancermetastasisthroughadhesiontogalectinsinthemetastaticniche AT bhatiasangeetan aberrantglycosylationpromoteslungcancermetastasisthroughadhesiontogalectinsinthemetastaticniche |