Center for Molecular Medicine, Faculty of Medicine, University of Kragujevac, Svetozara Markovica 69, 34000, Kragujevac, Serbia.
Clin Exp Metastasis. 2011 Jun;28(5):451-62. doi: 10.1007/s10585-011-9383-y. Epub 2011 Mar 26.
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.
半乳糖凝集素-3（Galectin-3）是一种β半乳糖苷结合凝集素，在与肿瘤发生相关的过程中发挥重要作用，如恶性细胞转化、侵袭和转移。我们研究了宿主中 Galectin-3 的缺失是否会影响 B16F1 恶性黑色素瘤的转移。通过肺部转移灶的数量和大小评估，Galectin-3 缺失（Gal-3(-/-)）小鼠对转移性恶性黑色素瘤的抵抗力更强。体外实验显示，Gal-3(-/-)小鼠组织切片中附着的恶性细胞数量较少。此外，Galectin-3 的缺失与荷瘤宿主中 IFN-γ 和 IL-17 血清水平升高相关。有趣的是，注射 B16F1 黑色素瘤细胞后，Gal-3(-/-)小鼠的脾脏中 Foxp3(+)T 细胞数量较低。最后，我们发现，虽然 CD8(+)T 细胞和黏附细胞的细胞毒性相似，但 Gal-3(-/-)小鼠脾 NK 细胞的细胞毒性活性高于“野生型”（Gal-3( +/+ )）小鼠。尽管 CD3ε(-)NK1.1(+)的总数减少，Gal-3(-/-)小鼠持续具有显著更高比例的有效细胞毒性 CD27(high)CD11b(high)NK 细胞以及未成熟的 CD27(high)CD11b(low)NK 细胞的比例。相比之下，Gal-3( +/+ )小鼠中 CD27(low)CD11b(high)功能衰竭更少的 NK 细胞和携带抑制性 KLRG1 受体的 NK 细胞数量更多。似乎 Galectin-3 的缺失通过至少两种独立的机制影响肿瘤转移：通过减少黑色素瘤细胞与靶组织的结合以及通过增强 NK 介导的抗肿瘤反应，表明 Galectin-3 可能被视为治疗靶点。
