Becker Jürgen, Covelo-Fernandez Ana, von Bonin Frederike, Kube Dieter, Wilting Jörg
Department of Anatomy and Cell Biology, University Medicine Goettingen, 37075 Goettingen, Germany.
Department of Hematology and Oncology, University Medicine Goettingen, 37075 Goettingen, Germany.
Vasc Cell. 2012 Mar 9;4(1):3. doi: 10.1186/2045-824X-4-3.
Burkitt's lymphoma (BL) is an aggressive Non-Hodgkin lymphoma. Epstein-Barr Virus (EBV) is able to transform B cells and is a causative infectious agent in BL. The precise role of EBV in lymphoma progression is still unclear. Most investigations have concentrated on cell autonomous functions of EBV in B cells. Functions of the local environment in BL progression have rarely been studied, mainly due to the lack of appropriate in vivo models. Therefore, we inoculated different human BL cell-lines onto the chorioallantoic membrane (CAM) of embryonic day 10 (ED10) chick embryos and re-incubated until ED14 and ED17.
All cell-lines formed solid tumors. However, we observed strong differences in the behavior of EBV+ and EBV- cell-lines. Tumor borders of EBV+ cells were very fuzzy and numerous cells migrated into the CAM. In EBV- tumors, the borders were much better defined. In contrast to EBV- cells, the EBV+ cells induced massive immigration of chick leukocytes at the tumor borders and the development of granulation tissue with large numbers of blood vessels and lymphatics, although the expression of pro- and anti-angiogenic forms of Vascular Endothelial Growth Factors/receptors was the same in all BL cell-lines tested. The EBV+ cell-lines massively disseminated via the lymphatics and completely occluded them.
Our data suggest that the EBV+ cells attract pro-angiogenic leukocytes, which then induce secondary tumor-stroma interactions contributing to the progression of BL. We show that the CAM is a highly suitable in vivo model to study the differential behavior of BL cell-lines.
伯基特淋巴瘤（BL）是一种侵袭性非霍奇金淋巴瘤。爱泼斯坦-巴尔病毒（EBV）能够转化B细胞，是BL的一种致病性感染因子。EBV在淋巴瘤进展中的具体作用仍不清楚。大多数研究集中在EBV在B细胞中的细胞自主功能。BL进展中局部环境的功能很少被研究，主要是由于缺乏合适的体内模型。因此，我们将不同的人BL细胞系接种到胚胎第10天（ED10）鸡胚的绒毛尿囊膜（CAM）上，并重新孵育至ED14和ED17。
所有细胞系均形成实体瘤。然而，我们观察到EBV阳性和EBV阴性细胞系的行为存在显著差异。EBV阳性细胞的肿瘤边界非常模糊，大量细胞迁移到CAM中。在EBV阴性肿瘤中，边界更清晰。与EBV阴性细胞不同，EBV阳性细胞在肿瘤边界诱导鸡白细胞大量迁移，并形成具有大量血管和淋巴管的肉芽组织，尽管在所有测试的BL细胞系中血管内皮生长因子/受体的促血管生成和抗血管生成形式的表达相同。EBV阳性细胞系通过淋巴管大量扩散并完全阻塞它们。
我们的数据表明，EBV阳性细胞吸引促血管生成的白细胞，然后诱导继发性肿瘤-基质相互作用，促进BL的进展。我们表明，CAM是研究BL细胞系差异行为的高度合适的体内模型。
