Troncoso María F, Ferragut Fátima, Bacigalupo María L, Cárdenas Delgado Víctor M, Nugnes Lorena G, Gentilini Lucas, Laderach Diego, Wolfenstein-Todel Carlota, Compagno Daniel, Rabinovich Gabriel A, Elola María T
Instituto de Química y Fisicoquímica Biológicas Prof. Dr. Alejandro Paladini (UBA-CONICET), Facultad de Farmacia y Bioquímica.
Laboratorio de Glicómica Funcional, IQUIBICEN-CONICET, Departamento de Química Biológica. Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
Glycobiology. 2014 Oct;24(10):907-14. doi: 10.1093/glycob/cwu054. Epub 2014 Jun 16.
Galectin-8 (gal-8) is a "tandem-repeat"-type galectin, containing two carbohydrate recognition domains connected by a linker peptide. gal-8 is expressed both in the cytoplasm and nucleus in vascular endothelial cells (ECs) from normal and tumor-associated blood vessels, and in lymphatic endothelial cells. Herein, we describe a novel role for gal-8 in the regulation of vascular and lymphatic angiogenesis and provide evidence of its critical implications in tumor biology. Functional assays revealed central roles for gal-8 in the control of capillary-tube formation, EC migration and in vivo angiogenesis. So far, two endothelial ligands have been described for gal-8, namely podoplanin in lymphatic vessels and CD166 (ALCAM, activated leukocyte cell adhesion molecule) in vascular ECs. Other related gal-8 functions are also summarized here, including cell adhesion and migration, which collectively demonstrate the multi-functionality of this complex lectin. Thus, gal-8 is an important component of the angiogenesis network, and an essential molecule in the extracellular matrix by providing molecular anchoring to this surrounding matrix. The implications of gal-8 in tumor angiogenesis remain to be further explored, but it is exciting to speculate that modulating gal-8-glycan interactions could be used to block lymphatic-vascular connections vital for metastasis.
半乳糖凝集素-8（gal-8）是一种“串联重复”型半乳糖凝集素，包含两个通过连接肽相连的碳水化合物识别结构域。gal-8在正常血管和肿瘤相关血管的血管内皮细胞（ECs）的细胞质和细胞核中均有表达，在淋巴管内皮细胞中也有表达。在此，我们描述了gal-8在调节血管和淋巴管生成中的新作用，并提供了其在肿瘤生物学中关键作用的证据。功能分析揭示了gal-8在控制毛细血管形成、EC迁移和体内血管生成中的核心作用。到目前为止，已描述了gal-8的两种内皮细胞配体，即淋巴管中的血小板反应蛋白和血管ECs中的CD166（活化白细胞细胞粘附分子，ALCAM）。本文还总结了gal-8的其他相关功能，包括细胞粘附和迁移，这些共同证明了这种复杂凝集素的多功能性。因此，gal-8是血管生成网络的重要组成部分，并且通过为周围基质提供分子锚定而成为细胞外基质中的必需分子。gal-8在肿瘤血管生成中的意义仍有待进一步探索，但推测调节gal-8-聚糖相互作用可用于阻断对转移至关重要的淋巴管连接是令人兴奋的。
