N-glycans and metastasis in galectin-3 transgenic mice

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.