Division of Surgical Oncology, Department of Surgery, Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd, Dallas, TX, 75390-8593, USA.
Cell Mol Life Sci. 2014 Jan;71(2):299-309. doi: 10.1007/s00018-013-1432-z. Epub 2013 Aug 4.
Pericytes are critical for vascular morphogenesis and contribute to several pathologies, including cancer development and progression. The mechanisms governing pericyte migration and differentiation are complex and have not been fully established. Current literature suggests that platelet-derived growth factor/platelet-derived growth factor receptor-β, sphingosine 1-phosphate/endothelial differentiation gene-1, angiopoietin-1/tyrosine kinase with immunoglobulin-like and EGF-like domains 2, angiopoietin-2/tyrosine kinase with immunoglobulin-like and EGF-like domains 2, transforming growth factor β/activin receptor-like kinase 1, transforming growth factor β/activin receptor-like kinase 5, Semaphorin-3A/Neuropilin, and matrix metalloproteinase activity regulate the recruitment of pericytes to nascent vessels. Interestingly, many of these pathways are directly affected by secreted protein acidic and rich in cysteine (SPARC). Here, we summarize the function of these factors in pericyte migration and discuss if and how SPARC might influence these activities and thus provide an additional layer of control for the recruitment of vascular support cells. Additionally, the consequences of targeted inhibition of pericytes in tumors and the current understanding of pericyte recruitment in pathological environments are discussed.
周细胞对于血管形态发生至关重要,并与多种病理学相关,包括癌症的发生和进展。调控周细胞迁移和分化的机制非常复杂,尚未完全阐明。目前的文献表明,血小板衍生生长因子/血小板衍生生长因子受体-β、1-磷酸鞘氨醇/内皮分化基因-1、血管生成素-1/含免疫球蛋白样和表皮生长因子样结构域酪氨酸激酶 2、血管生成素-2/含免疫球蛋白样和表皮生长因子样结构域酪氨酸激酶 2、转化生长因子β/激活素受体样激酶 1、转化生长因子β/激活素受体样激酶 5、神经丝氨酸蛋白 3A/神经纤毛蛋白和基质金属蛋白酶活性调节周细胞向新生血管的募集。有趣的是,这些途径中的许多都直接受到富含半胱氨酸的酸性分泌蛋白(SPARC)的影响。在这里,我们总结了这些因子在周细胞迁移中的作用,并讨论了 SPARC 是否可能影响这些活性,从而为血管支持细胞的募集提供额外的控制层。此外,还讨论了在肿瘤中靶向抑制周细胞的后果以及目前对病理环境中周细胞募集的理解。