N-glycans and metastasis in galectin-3 transgenic mice

More, Shyam K, Srinivasan, Nithya, Budnar, Srikanth, Bane, Sanjay M, Upadhya, Archana, Thorat, Rahul A, Ingle, Arvind D, Chiplunkar, Shubhada V and Kalraiya, Rajiv D (2015) N-glycans and metastasis in galectin-3 transgenic mice. Biochemical and Biophysical Research Communications, 460 2: 302-307. doi:10.1016/j.bbrc.2015.03.030

Author More, Shyam K
Srinivasan, Nithya
Budnar, Srikanth
Bane, Sanjay M
Upadhya, Archana
Thorat, Rahul A
Ingle, Arvind D
Chiplunkar, Shubhada V
Kalraiya, Rajiv D
Title N-glycans and metastasis in galectin-3 transgenic mice
Journal name Biochemical and Biophysical Research Communications   Check publisher's open access policy
ISSN 1090-2104
Publication date 2015-05-01
Year available 2015
Sub-type Article (original research)
DOI 10.1016/j.bbrc.2015.03.030
Open Access Status Not Open Access
Volume 460
Issue 2
Start page 302
End page 307
Total pages 6
Place of publication Philadelphia, United States
Publisher Elsevier Inc
Language eng
Formatted abstract
Poly-N-acetyl-lactosamine (polyLacNAc) on N-glycans facilitate lung specific metastasis of melanoma cells by serving as high affinity ligands for galectin-3, expressed in highest amounts in the lungs, on almost all its tissue compartments including on the surface of vascular endothelium. PolyLacNAc not only aids in initial arrest on the organ endothelium but in all the events of extravasation. Inhibition of polyLacNAc synthesis, or competitive inhibition of its interaction with galectin-3 all inhibited these processes and experimental metastasis. Transgenic galectin-3 mice, viz., gal-3+/+ (wild type), gal-3+/− (hemizygous) and gal-3−/− (null) have been used to prove that galectin-3/polyLacNAc interactions are indeed critical for lung specific metastasis.

Gal-3+/− mice which showed <50% expression of galectin-3 on the lungs also showed proportionate decrease in the number of B16F10 melanoma metastatic colonies affirming that galectin-3 and polyLacNAc interactions are indeed key determinants of lung metastasis. However, surprisingly, the number and size of metastatic colonies in gal-3−/− mice was very similar as that seen in gal-3+/+ mice. The levels of lactose binding lectins on the lungs and the transcripts of other galectins (galectin-1, -8 and -9) which are expressed on lungs and have similar sugar binding specificities as galectins-3, remain unchanged in gal-3+/+ and gal-3−/− mice. Further, inhibition of N-glycosylation with Swainsonine (SW) which drastically reduces metastasis of B16F10 cells in gal-3+/+ mice, did not affect lung metastasis when assessed in gal-3−/− mice. Together, these results rule out the possibility of some other galectin taking over the function of galectin-3 in gal-3−/− mice. Chimeric mice generated to assess if absence of any effect on metastasis is due to compromised tumor immunity by replacing bone marrow of gal-3−/− mice with that from gal-3+/+ mice, also failed to impact melanoma metastasis. As galectin-3 regulates several immune functions including maturation of different immune cells, compromised tumor immunity could be the major determinant of melanoma metastasis in gal-3−/− mice and warrants thorough investigation.
Keyword Galectin-3
Organ specific metastasis
Galectin-3 transgenic mice
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
Institute for Molecular Bioscience - Publications
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