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Research Article

淋巴管生成因子CCBE1促进结直肠癌血管生成和肿瘤生长

卷 22, 期 9, 2022

发表于: 14 January, 2022

页: [819 - 825] 页: 7

弟呕挨: 10.2174/1566524021666211124092804

价格: $65

摘要

背景:胶原和钙结合EGF结构域-1 （CCBE1）对淋巴管系统和结直肠癌（CRC）淋巴管生成的发展至关重要，因为它增强了血管内皮生长因子C （VEGFC）激活VEGFR3的蛋白水解过程。完全加工成熟的VEGFC还可以激活VEGFR2, VEGFR2是一种重要的内皮特异性受体酪氨酸激酶，参与血管发育和肿瘤血管生成。然而，CCBE1在肿瘤血管生成中的作用尚不明确。 方法:本研究发现CCBE1蛋白在伴远处转移的原发性结直肠癌组织中表达较高，且与血管密度呈正相关。 结果:CCBE1 mRNA表达与TCGA数据集中的CRC中血管内皮标志物CD31和VEGFR2密切相关。CCBE1过表达的结直肠癌细胞系HCT116的上清液在体外可显著促进人脐静脉内皮细胞（HUVECs）的成管能力，在体内可促进血管生成和肿瘤生长。CCBE1基因的下调降低了CRC的血管生成能力。 结论:我们的结果证明了CCBE1在CRC中的血管生成作用。

关键词: 血管生成，CCBE1，结直肠癌，VEGFC, VEGFR2，肿瘤生长。

« Previous Next »
[1]
De Palma M, Biziato D, Petrova TV. Microenvironmental regulation of tumour angiogenesis. Nat Rev Cancer 2017; 17(8): 457-74.
[http://dx.doi.org/10.1038/nrc.2017.51] [PMID: 28706266]
[2]
La Porta S, Roth L, Singhal M, et al. Endothelial Tie1-mediated angiogenesis and vascular abnormalization promote tumor progression and metastasis. J Clin Invest 2018; 128(2): 834-45.
[http://dx.doi.org/10.1172/JCI94674] [PMID: 29355844]
[3]
Varney ML, Singh S, Backora M, Chen Z, Singh RK. Lymphangiogenesis and anti-tumor immune responses. Curr Mol Med 2009; 9(6): 694-701.
[http://dx.doi.org/10.2174/156652409788970733] [PMID: 19689296]
[4]
Olsson AK, Dimberg A, Kreuger J, Claesson-Welsh L. VEGF receptor signalling - in control of vascular function. Nat Rev Mol Cell Biol 2006; 7(5): 359-71.
[http://dx.doi.org/10.1038/nrm1911] [PMID: 16633338]
[5]
Zheng W, Aspelund A, Alitalo K. Lymphangiogenic factors, mechanisms, and applications. J Clin Invest 2014; 124(3): 878-87.
[http://dx.doi.org/10.1172/JCI71603] [PMID: 24590272]
[6]
Zhao Y, Adjei AA. Targeting angiogenesis in cancer therapy: Moving beyond vascular endothelial growth factor. Oncologist 2015; 20(6): 660-73.
[http://dx.doi.org/10.1634/theoncologist.2014-0465] [PMID: 26001391]
[7]
Alders M, Hogan BM, Gjini E, et al. Mutations in CCBE1 cause generalized lymph vessel dysplasia in humans. Nat Genet 2009; 41(12): 1272-4.
[http://dx.doi.org/10.1038/ng.484] [PMID: 19935664]
[8]
Hogan BM, Bos FL, Bussmann J, et al. Ccbe1 is required for embryonic lymphangiogenesis and venous sprouting. Nat Genet 2009; 41(4): 396-8.
[http://dx.doi.org/10.1038/ng.321] [PMID: 19287381]
[9]
Jeltsch M, Jha SK, Tvorogov D, et al. CCBE1 enhances lymphangiogenesis via A disintegrin and metalloprotease with thrombospondin motifs-3-mediated vascular endothelial growth factor-C activation. Circulation 2014; 129(19): 1962-71.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.113.002779] [PMID: 24552833]
[10]
Joukov V, Pajusola K, Kaipainen A, et al. A novel vascular endothelial growth factor, VEGF-C, is a ligand for the Flt4 (VEGFR-3) and KDR (VEGFR-2) receptor tyrosine kinases. EMBO J 1996; 15(2): 290-8.
[http://dx.doi.org/10.1002/j.1460-2075.1996.tb00359.x] [PMID: 8617204]
[11]
Joukov V, Sorsa T, Kumar V, et al. Proteolytic processing regulates receptor specificity and activity of VEGF-C. EMBO J 1997; 16(13): 3898-911.
[http://dx.doi.org/10.1093/emboj/16.13.3898] [PMID: 9233800]
[12]
Song J, Chen W, Cui X, et al. CCBE1 promotes tumor lymphangiogenesis and is negatively regulated by TGFβ signaling in colorectal cancer. Theranostics 2020; 10(5): 2327-41.
[http://dx.doi.org/10.7150/thno.39740] [PMID: 32089745]
[13]
Le Guen L, Karpanen T, Schulte D, et al. Ccbe1 regulates Vegfc-mediated induction of Vegfr3 signaling during embryonic lymphangiogenesis. Development 2014; 141(6): 1239-49.
[http://dx.doi.org/10.1242/dev.100495] [PMID: 24523457]
[14]
Parab S, Quick RE, Matsuoka RL. Endothelial cell-type-specific molecular requirements for angiogenesis drive fenestrated vessel development in the brain. eLife 2021; 10: 10.
[http://dx.doi.org/10.7554/eLife.64295] [PMID: 33459592]
[15]
Bonet F, Pereira PNG, Bover O, Marques S, Inácio JM, Belo JA. CCBE1 is required for coronary vessel development and proper coronary artery stem formation in the mouse heart. Dev Dyn 2018; 247(10): 1135-45.
[http://dx.doi.org/10.1002/dvdy.24670] [PMID: 30204931]
[16]
Silva MM, Gomes-Alves P, Rosa S, et al. Full-length human CCBE1 production and purification: Leveraging bioprocess development for high quality glycosylation attributes and functionality. J Biotechnol 2018; 285: 6-14.
[http://dx.doi.org/10.1016/j.jbiotec.2018.08.015] [PMID: 30165116]
[17]
Tian GA, Zhu CC, Zhang XX, et al. CCBE1 promotes GIST development through enhancing angiogenesis and mediating resistance to imatinib. Sci Rep 2016; 6: 31071.
[http://dx.doi.org/10.1038/srep31071] [PMID: 27506146]

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