Tang J-C, Xie A-Y, Cai X-J
Mol Biol (Mosk). 2014 Nov-Dec;48(6):875-80. doi: 10.7868/s0026898414060172.
Altered interactions between the extracellular matrix and cells play an important part in tumorigenesis and metastasis. As a member of matricellular glycoprotein, fibulin-5 is expressed in elastin-rich tissues and organizes the matrix structures by interacting with many extracellular proteins. Fibulin-5 expression is closely associated with normal embryonic development and organogenesis. Mice deficient for the fibulin-5 gene exhibit systemic elastic fiber defects with manifestation of loose skin, emphysematous lung and tortuous vessels. Additionally, fibulin-5 null mice exhibited increased angiogenesis after wound healing or PVA sponge implantation and matrigel implantation experiments show fibulin-5 inhibited vessel formation, suggesting fibulin-5 functions as an angiogenesis inhibitor. Fibulin-5 also plays critical roles in proliferation, migration and invasion of certain tumors, and the effect of fibulin-5 on tumorigenesis appears to be largely context-dependent. This effect might involve the inhibiting action of fibulin-5 on angiogenesis. This review focuses on recent advances in our understanding of the roles of fibulin-5 in tumorigenesis: both tumor promoting and suppressing activity of fibulin-5 are reviewed, and the emerging evidences of its promising potential as therapeutic options and/or targets in the treatment of cancer also highlighted.
细胞外基质与细胞之间相互作用的改变在肿瘤发生和转移中起重要作用。作为基质细胞糖蛋白的一员，纤连蛋白-5在富含弹性蛋白的组织中表达，并通过与许多细胞外蛋白相互作用来组织基质结构。纤连蛋白-5的表达与正常胚胎发育和器官发生密切相关。缺乏纤连蛋白-5基因的小鼠表现出全身性弹性纤维缺陷，表现为皮肤松弛、肺气肿和血管迂曲。此外，纤连蛋白-5基因敲除小鼠在伤口愈合后或聚乙烯醇海绵植入后血管生成增加，基质胶植入实验表明纤连蛋白-5抑制血管形成，提示纤连蛋白-5作为血管生成抑制剂发挥作用。纤连蛋白-5在某些肿瘤的增殖、迁移和侵袭中也起关键作用，纤连蛋白-5对肿瘤发生的影响似乎很大程度上取决于具体情况。这种影响可能涉及纤连蛋白-5对血管生成的抑制作用。本综述重点介绍了我们对纤连蛋白-5在肿瘤发生中作用的最新认识进展：综述了纤连蛋白-5的促肿瘤和抑肿瘤活性，并强调了其作为癌症治疗的有前景的治疗选择和/或靶点的新证据。
