Macrophages enhance Vegfa-driven angiogenesis in an embryonic zebrafish tumour xenograft model.
Macrophages enhance Vegfa-driven angiogenesis in an embryonic zebrafish tumour xenograft model.
复制标题
巨噬细胞增强胚胎斑马鱼肿瘤异种移植模型中 Vegfa 驱动的血管生成。
DOI：
10.1242/dmm.035998
复制
发表时间：
2018-11-29
影响因子：
4.3
通讯作者：
Astin JW
中科院分区：
文献类型：
--
作者：
Britto DD;Wyroba B;Chen W;Lockwood RA;Tran KB;Shepherd PR;Hall CJ;Crosier KE;Crosier PS;Astin JW
肿瘤血管生成长期以来一直是抗癌治疗的焦点;然而，抗血管生成癌症治疗策略的临床成功有限。肿瘤相关骨髓细胞被认为在癌症对抗血管生成疗法的抗性中起作用，但它们这样做的机制尚不清楚。已经开发了胚胎斑马鱼异种移植模型来研究肿瘤血管生成的机制，并作为筛选抗血管生成化合物的测定。在这项研究中，我们使用细胞消融技术去除巨噬细胞或中性粒细胞，并通过定量移植物血管化水平来评估它们对斑马鱼异种移植物血管生成的贡献。消融巨噬细胞而非中性粒细胞导致肿瘤异种移植物血管形成大幅减少，延时成像表明肿瘤异种移植物巨噬细胞与发展中肿瘤血管的迁移尖端直接相关。最后，我们发现，尽管巨噬细胞是分泌VEGFA或过表达斑马鱼vegfaa的异种移植物血管化所必需的，但它们不是低水平VEGFA移植物血管化所必需的，这表明斑马鱼巨噬细胞可以增强Vegfa驱动的肿瘤血管生成。巨噬细胞对这种血管生成反应的重要性表明，该模型可用于进一步研究骨髓细胞和肿瘤血管形成之间的相互作用。摘要：斑马鱼胚胎巨噬细胞与肿瘤异种移植血管的远端相关，并且是Vegfa驱动的血管生成所需的。
Tumour angiogenesis has long been a focus of anti-cancer therapy; however, anti-angiogenic cancer treatment strategies have had limited clinical success. Tumour-associated myeloid cells are believed to play a role in the resistance of cancer towards anti-angiogenesis therapy, but the mechanisms by which they do this are unclear. An embryonic zebrafish xenograft model has been developed to investigate the mechanisms of tumour angiogenesis and as an assay to screen anti-angiogenic compounds. In this study, we used cell ablation techniques to remove either macrophages or neutrophils and assessed their contribution towards zebrafish xenograft angiogenesis by quantitating levels of graft vascularisation. The ablation of macrophages, but not neutrophils, caused a strong reduction in tumour xenograft vascularisation and time-lapse imaging demonstrated that tumour xenograft macrophages directly associated with the migrating tip of developing tumour blood vessels. Finally, we found that, although macrophages are required for vascularisation in xenografts that either secrete VEGFA or overexpress zebrafish vegfaa, they are not required for the vascularisation of grafts with low levels of VEGFA, suggesting that zebrafish macrophages can enhance Vegfa-driven tumour angiogenesis. The importance of macrophages to this angiogenic response suggests that this model could be used to further investigate the interplay between myeloid cells and tumour vascularisation. Summary: Zebrafish embryonic macrophages associate with the distal tips of tumour xenograft blood vessels and are required for Vegfa-driven angiogenesis.
登录
查看更多内容
影响因子：
56.9
作者：
Asahara, T;Murohara, T;Isner, JM
通讯作者：
Isner, JM
肿瘤相关巨噬细胞促进肿瘤进展的新机制：最新研究进展和肿瘤免疫治疗的潜在靶点
影响因子：
4.1
作者：
Guo Q;Jin Z;Yuan Y;Liu R;Xu T;Wei H;Xu X;He S;Chen S;Shi Z;Hou W;Hua B
通讯作者：
Hua B
影响因子：
7.3
作者：
Albini A;Bruno A;Noonan DM;Mortara L
通讯作者：
Mortara L
影响因子：
2.7
作者：
Davison, Jon M.;Akitake, Courtney M.;Parsons, Michael J.
通讯作者：
Parsons, Michael J.
影响因子：
50.3
作者：
Casanovas, O;Hicklin, DJ;Hanahan, D
通讯作者：
Hanahan, D