Deletion of galectin-3 in the host attenuates metastasis of murine melanoma by modulating tumor adhesion and NK cell activity

作者：Radosavljevic Gordana; Jovanovic Ivan; Majstorovic Ivana; Mitrovic Maja; Lisnic Vanda Juranic; Arsenijevic Nebojsa; Jonjic Stipan; Lukic Miodrag L^*

来源：Clinical & Experimental Metastasis, 2011, 28(5): 451-462.

DOI：10.1007/s10585-011-9383-y

• B16F1
• Galectin-3
• Malignant melanoma
• Metastasis
• NK cells

Galectin-3, a beta 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-gamma 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 CD3 epsilon(-)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.

• 出版日期2011-6
• 单位中国人民解放军军事医学科学院