Deletion of galectin-3 in the host attenuates metastasis of murine melanoma by modulating tumor adhesion and NK cell activity
| Autor: | Nebojsa Arsenijevic, Gordana Radosavljevic, Ivana Majstorovic, Stipan Jonjić, Miodrag L. Lukic, Ivan Jovanovic, Maja Mitrović, Vanda Juranić Lisnić |
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| Rok vydání: | 2011 |
| Předmět: |
Male
tumor Cancer Research Galectin 3 T cell Biology Mice 03 medical and health sciences Interleukin 21 0302 clinical medicine Cell Adhesion melanoma medicine Animals metastasis Cytotoxic T cell Neoplasm Metastasis Cell adhesion 030304 developmental biology 0303 health sciences Lymphokine-activated killer cell Melanoma BIOMEDICINE AND HEALTHCARE. Basic Medical Sciences gal-3 nk cell General Medicine Gal-3 medicine.disease 3. Good health Killer Cells Natural Mice Inbred C57BL medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Interleukin 12 Cancer research Female BIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti Gene Deletion CD8 |
| Zdroj: | Clinical & experimental metastasis Volume 28 Issue 5 |
| ISSN: | 1573-7276 0262-0898 |
| Popis: | 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 CD3e−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. |
| Databáze: | OpenAIRE |
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