Programa de Glicobiologia, Laboratório de Bioquímica e Biologia Celular de Glicoconjugados, Instituto de Bioquímica Médica Leopoldo de Meis, Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro , Rio de Janeiro , Brazil.
Front Oncol. 2014 Jun 16;4:138. doi: 10.3389/fonc.2014.00138. eCollection 2014.
Galectin-3, the only chimera galectin found in vertebrates, is one of the best-studied galectins. It is expressed in several cell types and is involved in a broad range of physiological and pathological processes, such as cell adhesion, cell activation and chemoattraction, cell cycle, apoptosis, and cell growth and differentiation. However, this molecule raises special interest due to its role in regulating cancer cell activities. Galectin-3 has high affinity for β-1,6-N-acetylglucosamine branched glycans, which are formed by the action of the β1,6-N-acetylglucosaminyltransferase V (Mgat5). Mgat5-related changes in protein/lipid glycosylation on cell surface lead to alterations in the clustering of membrane proteins through lattice formation, resulting in functional advantages for tumor cells. Galectin-3 presence enhances migration and/or invasion of many tumors. Galectin-3-dependent clustering of integrins promotes ligand-induced integrin activation, leading to cell motility. Galectin-3 binding to mucin-1 increases transendothelial invasion, decreasing metastasis-free survival in an experimental metastasis model. Galectin-3 also affects endothelial cell behavior by regulating capillary tube formation. This lectin is found in the tumor stroma, suggesting a role for microenvironmental galectin-3 in tumor progression. Galectin-3 also seems to be involved in the recruitment of tumor-associated macrophages, possibly contributing to angiogenesis and tumor growth. This lectin can be a relevant factor in turning bone marrow in a sanctuary for leukemia cells, favoring resistance to therapy. Finally, galectin-3 seems to play a relevant role in orchestrating distinct cell events in tumor microenvironment and for this reason, it can be considered a target in tumor therapies. In conclusion, this review aims to describe the processes of tumor progression and metastasis involving extracellular galectin-3 and its expression and regulation.
半乳糖凝集素-3 是脊椎动物中唯一发现的嵌合半乳糖凝集素，是研究最深入的半乳糖凝集素之一。它在多种细胞类型中表达，并参与广泛的生理和病理过程，如细胞黏附、细胞激活和趋化、细胞周期、细胞凋亡、细胞生长和分化。然而，由于其在调节癌细胞活性方面的作用，该分子引起了特别的兴趣。半乳糖凝集素-3 对半乳糖凝集素-3 具有高亲和力β-1,6-N-乙酰葡萄糖胺支链聚糖，该聚糖由β1,6-N-乙酰葡萄糖胺基转移酶 V（Mgat5）作用形成。Mgat5 相关的细胞表面蛋白/脂聚糖糖基化改变导致通过晶格形成改变膜蛋白的聚集，从而为肿瘤细胞提供功能优势。半乳糖凝集素-3 的存在增强了许多肿瘤的迁移和/或侵袭。半乳糖凝集素-3 依赖性整合素聚集促进配体诱导的整合素激活，导致细胞迁移。半乳糖凝集素-3 与粘蛋白-1 的结合增加了跨内皮侵袭，减少了实验转移模型中的无转移生存。半乳糖凝集素-3 还通过调节毛细血管形成来影响内皮细胞行为。这种凝集素存在于肿瘤基质中，表明微环境中的半乳糖凝集素-3 在肿瘤进展中起作用。半乳糖凝集素-3 似乎还参与招募肿瘤相关巨噬细胞，可能有助于血管生成和肿瘤生长。这种凝集素可能是使骨髓成为白血病细胞避难所的相关因素，有利于对治疗的耐药性。最后，半乳糖凝集素-3 似乎在协调肿瘤微环境中不同的细胞事件中发挥着重要作用，因此可以被认为是肿瘤治疗的一个靶点。总之，本综述旨在描述涉及细胞外半乳糖凝集素-3 及其表达和调节的肿瘤进展和转移的过程。
