Lack of Angiogenesis in Experimental Brain Metastases
Lack of Angiogenesis in Experimental Brain Metastases
复制标题
DOI：
10.1097/nen.0b013e318233afd7
复制
发表时间：
2011-11-01
影响因子：
3.2
通讯作者：
Paku, Sandor
中科院分区：
文献类型：
--
作者：
Bugyik, Edina;Dezsoe, Katalin;Paku, Sandor
人们认为血管生成对于脑中转移性肿瘤的生长至关重要。我们分析了注射到小鼠大脑中的 4 种上皮细胞系（C38、ZR75、HT25 和 H1650）和纤维肉瘤（HT1080）细胞系形成的肿瘤的血管化。没有观察到瘤周血管生成。肿瘤显然是通过合并原生血管而获得脉管系统的。与瘤周组织相比，所有肿瘤内的血管密度较低，但血管直径和血管细胞增殖较高。合并血管的数量与血管细胞增殖之间存在负相关。与侵袭性肿瘤相比，具有推动生长模式的上皮肿瘤具有较低的血管密度和较高的血管细胞增殖。合并的血管保留了其正常结构，但星形胶质细胞足突被肿瘤细胞取代。附着于血管基底膜导致 ZR75 乳腺癌细胞分化。在HT1080转移瘤中，存在套叠性血管生成，即附着在血管上的纤维肉瘤细胞引起管腔分裂并填充正在发育的柱。在肿瘤或对照脑伤口中均未观察到分支血管生成。这些数据表明，脑转移瘤的早期生长不需要萌芽血管生成，并且该模型中的肿瘤生长是宿主血管合并的结果。
Angiogenesis is believed to be essential for the growth of metastatic tumors in the brain. We analyzed the vascularization of tumors formed by 4 epithelial cell lines (C38, ZR75, HT25, and H1650) and a fibrosarcoma (HT1080) cell line injected into the brains of mice. No peritumoral angiogenesis was observed. Tumors apparently acquired their vasculature by incorporation of native vessels. Vessel density was lower, but vessel diameter and vascular cell proliferation were higher within all tumors versus those in the peritumoral tissue. There was an inverse correlation between the number of incorporated vessels and vascular cell proliferation. Epithelial tumors with pushing growth patterns had lower vessel density and elevated vascular cell proliferation compared with invasive tumors. The incorporated vessels retained their normal structure, with the exception of astrocyte foot processes that were replaced by tumor cells. Attachment to the vascular basement membrane led to the differentiation of the ZR75 breast cancer cells. In the HT1080 metastases, there was intussusceptive angiogenesis, that is, the fibrosarcoma cells that were attached to the vessel caused lumen splitting and filled the developing pillars. Branching angiogenesis was not observed either in the tumors or in control cerebral wounds. These data suggest that sprouting angiogenesis is not needed for the incipient growth of cerebral metastases and that tumor growth in this model is a result of incorporation of host vessels.