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

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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 CD27highCD11bhigh NK cells as well as the percentage of immature CD27highCD11blow NK cells. In contrast, CD27lowCD11bhigh 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.

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Abbreviations

B16F1:

Murine skin melanoma cell line

Gal-3:

Galectin-3

IFN-γ:

Interferon-gamma

IL-17:

Interleukin-17

IL-4:

Interleukin-4

KLRG1:

Killer cell lectin-like receptor G1

NK cells:

Natural killer cells

TNF-α:

Tumor necrosis-alpha

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Acknowledgments

This work was supported by grants from the Ministry of Science and Technological Development (project number 175071 and 175069), Serbia and from the Croatian Ministry of Science (0062004 and 0062007), Croatia. We thank Dragana Markovic and Milan Milojevic for excellent technical assistance.

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Authors and Affiliations

  1. Center for Molecular Medicine, Faculty of Medicine, University of Kragujevac, Svetozara Markovica 69, 34000, Kragujevac, Serbia

    Gordana Radosavljevic, Ivan Jovanovic, Nebojsa Arsenijevic & Miodrag L. Lukic

  2. Department of Histology and Embryiology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia

    Maja Mitrovic, Vanda Juranic Lisnic & Stipan Jonjic

  3. Military Medical Academy, Belgrade, Serbia

    Ivana Majstorovic

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  1. Gordana Radosavljevic
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  2. Ivan Jovanovic
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Correspondence to Miodrag L. Lukic.

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Radosavljevic, G., Jovanovic, I., Majstorovic, I. et al. Deletion of galectin-3 in the host attenuates metastasis of murine melanoma by modulating tumor adhesion and NK cell activity. Clin Exp Metastasis 28, 451–462 (2011). https://doi.org/10.1007/s10585-011-9383-y

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