title: Deletion of galectin-3 in the host attenuates metastasis of murine melanoma by modulating tumor adhesion and NK cell activity.
abstract: Galectin-3, a β galactoside-binding lectin, plays an important role in the processes relevant to tumorigenesis such as malignant cell transformation, invasion and metastasis. We have investigated whether deletion of Galectin-3 in the host affects the metastasis of B16F1 malignant melanoma. Galectin-3-deficient (Gal-3(-/-)) mice are more resistant to metastatic malignant melanoma as evaluated by number and size of metastatic colonies in the lung. In vitro assays showed lower number of attached malignant cells in the tissue section derived from Gal-3(-/-) mice. Furthermore, lack of Galectin-3 correlates with higher serum levels of IFN-γ and IL-17 in tumor bearing hosts. Interestingly, spleens of Gal-3(-/-) mice have lower number of Foxp3(+) T cells after injection of B16F1 melanoma cells. Finally, we found that while CD8(+) T cell and adherent cell cytotoxicity were similar, there was greater cytotoxic activity of splenic NK cells of Gal-3(-/-) mice compared with "wild-type" (Gal-3( +/+ )) mice. Despite the reduction in total number of CD3ε(-)NK1.1(+), Gal-3(-/-) mice constitutively have a significantly higher percentage of effective cytotoxic CD27(high)CD11b(high) NK cells as well as the percentage of immature CD27(high)CD11b(low) NK cells. In contrast, CD27(low)CD11b(high) less functionally exhausted NK cells and NK cells bearing inhibitory KLRG1 receptor were more numerous in Gal-3( +/+ ) mice. It appears that lack of Galectin-3 affects tumor metastasis by at least two independent mechanisms: by a decrease in binding of melanoma cells onto target tissue and by enhanced NK-mediated anti-tumor response suggesting that Galectin-3 may be considered as therapeutic target.
authors: Center for Molecular Medicine, Faculty of Medicine, University of Kragujevac, Svetozara Markovica 69, 34000, Kragujevac, Serbia.
authors: Gordana
authors: G
authors: Radosavljevic
authors: Ivan
authors: I
authors: Jovanovic
authors: Ivana
authors: I
authors: Majstorovic
authors: Maja
authors: M
authors: Mitrovic
authors: Vanda Juranic
authors: VJ
authors: Lisnic
authors: Nebojsa
authors: N
authors: Arsenijevic
authors: Stipan
authors: S
authors: Jonjic
authors: Miodrag L
authors: ML
authors: Lukic
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D005260:Female; D037502:Galectin 3 / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000276:immunology
chemical_list: D037502:Galectin 3; C485095:Lgals3 protein, mouse