Angiogenesis of liver metastases - Role of sinusoidal endothelial cells
Angiogenesis of liver metastases - Role of sinusoidal endothelial cells
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DOI：
10.1007/bf02237364
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发表时间：
2000-07-01
影响因子：
3.9
通讯作者：
Wexner, S
中科院分区：
文献类型：
--
作者：
Gervaz, P;Scholl, B;Wexner, S
目的：肿瘤诱导的血管生成需要来源于原有血管的内皮细胞的迁移和重塑。血管内皮生长因子是与结肠癌中新血管的发展最密切相关的生长因子。然而，血管内皮生长因子特异性受体flt-1和KDR mRNA的表达是不存在的血管内皮生长因子产生的继发性肝肿瘤周围的正常血窦血管。因此，肝窦内皮细胞在肝转移癌内新血管形成机制中的潜在作用仍不清楚。本研究的目的是确定窦状隙内皮细胞是否参与大肠癌肝转移的同基因模型中的肿瘤血管生成。方法：在摄取荧光探针标记的乙酰化低密度脂蛋白（双十八烷基吲哚羰花青）后，通过荧光显微镜鉴定窦内皮细胞。在实验开始时，在艾德IS大鼠中门静脉内注射100 μ L的双十八烷基-吲哚羰花青乙酰化低密度脂蛋白。两天后，在同系艾德IX大鼠中进行门静脉内注射10（7）DHD K12（一种化学诱导的结肠癌细胞系）。1周后处死动物，取肝脏进行常规组织学检查和免疫组化染色。结果：正常肝实质中，荧光与肝窦细胞相关，与大血管内皮无关。因此，特异性乙酰化低密度脂蛋白摄取允许肝窦内皮细胞从肝实质中存在的其他大血管内皮细胞中分化。在荷瘤肝脏中产生荧光的空间梯度。标记细胞聚集在转移灶的周围。当肿瘤生长超过200 μ m时，观察到新血管形成;荧光标记的细胞从外周侵入，这些细胞在瘤形成内排列成管状。结论：肝转移瘤血管内衬窦状内皮细胞。鉴定参与肿瘤间质区室形成的特定细胞类型具有重要意义。窦状隙内皮细胞表达特征明确的表面受体，在形态和代谢上与大血管内皮细胞不同。他们应该被认为是有吸引力的目标，为未来和现有的抗血管生成的策略，针对肝转移的间质室。
PURPOSE: Tumor-induced angiogenesis requires migration and remodeling of endothelial cells derived from preexisting blood vessels. Vascular endothelial growth factor is the growth factor most closely implicated in the development of neovessels in colon cancer. However, vascular endothelial growth factor-specific receptors flt-1 and KDR mRNA expression are absent in normal sinusoid vessels surrounding vascular endothelial growth factor-producing secondary hepatic tumors. Thus, the potential role of sinusoidal endothelial cells in the mechanism of neovessel formation within liver metastatic carcinomas remains unclear. The purpose of this study was to determine whether sinusoidal endothelial cells ate involved in tumor angiogenesis in a syngeneic model of liver metastases from colorectal cancer. METHODS: Sinusoidal endothelial cells were identified by fluorescence microscopy after uptake of acetylated low density lipoprotein labeled with a fluorescent probe (dioctadecyl-lindocarbocyanine). One hundred microliters of dioctadecyl-indocarbocyanine acetylated low density lipoprotein were injected intraportally at the start of experiment in ED IS rats. Two days later, intraportal injection of 10(7) DHD K12, a chemically induced colon carcinoma cell line, was performed in syngeneic ED IX rats. Animals were killed one week later and the livers were processed for routine histologic examination and immunohistochemistry using the mt endothelial cell antigen-I monoclonal antibody RESULTS: In normal parenchyma fluorescence was associated with sinusoidal cells but not with endothelium of large blood vessels. Thus, specific acetylated low density lipoprotein uptake allowed histologic;ll differentiation of sinusoidal endothelial cells from other large-vessel endothelial cells present in the hepatic parenchyma. In tumor-bearing liver a spatial gradient of fluorescence was generated. Labeled cells accumulated at the periphery of the metastases. When tumors grow beyond 200 mu m, neovessel formation was observed; there was an invasion of fluorescent-labeled cells from the periphery, which were arranged in a tubular formation within neoplasia. CONCLUSION: In liver metastases tumor vessels are lined with sinusoidal endothelial cells. Identification of a specific cell type involved in the formation of the stromal compartment of tumors has important implications. Sinusoidal endothelial cells express well-characterized surface receptors and differ morphologically and metabolically from large-vessel endothelia. They should be considered as attractive targets for future and existing antiangiogenic strategies directed against the stromal compartment of liver metastases.