Different pathways of macromolecule extravasation from hyperpermeable tumor vessels
Different pathways of macromolecule extravasation from hyperpermeable tumor vessels
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DOI：
10.1006/mvre.1999.2207
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发表时间：
2000-01-01
影响因子：
3.1
通讯作者：
Dvorak, HF
中科院分区：
文献类型：
--
作者：
Feng, D;Nagy, JA;Dvorak, HF
肿瘤微血管对血浆蛋白具有高渗透性，这是turner细胞分泌的血管渗透因子/血管内皮生长因子（VPF/VEGF）的结果。然而，大分子从肿瘤血管外渗的途径很少被研究。为了更精确地表征肿瘤血管并阐明大分子从血管外渗的途径，我们研究了两种明确的、分泌VPF/ vegf的小鼠癌，MOT和TA3/St。无论是在腹水中还是在实体形态中生长，MOT肿瘤都诱导了大的、缺乏周细胞的“母”血管，其内层内皮形成了窗，占表面的1.8-5.6%。窗的形成与内皮细胞囊泡细胞器（VVOs）的显著减少并行。TA3/St肿瘤比MOT肿瘤分泌更多的VPF/VEGF，诱导母血管VVOs不变且无窗。在这两种肿瘤中，血浆蛋白示踪剂铁蛋白通过VVOs外渗，在MOT肿瘤中铁蛋白也通过窗外渗。两例肿瘤均未见内皮间隙。因此，并非所有分泌VPF/ vegf的肿瘤都能诱导开孔内皮。此外，VVOs提供了一种内部膜储存，可以转移到内皮细胞表面，从而在MOT肿瘤中提供母血管形成所需的质膜的大量增加。在TA3/St肿瘤中，这种转移显然是不必要的，在TA3/St肿瘤中，广泛的早期内皮细胞分裂提供了形成母血管所需的质膜增加。(C) 2000年学术出版社。
Tumor microvessels are hyperpermeable to plasma proteins, a consequence of turner cell-secreted vascular permeability factor/vascular endothelial growth factor (VPF/VEGF). However, the pathways by which macromolecules extravasate from tumor vessels hare been little investigated. To characterize tumor vessels more precisely and to elucidate the pathways by which macromolecules extravasated from them, we studied two well-defined, VPF/VEGF-secreting murine carcinomas, MOT and TA3/St. Whether grown in ascites or solid form, MOT tumors induced large, pericyte-poor "mother" vessels whose lining endothelium developed fenestrae that involved 1.8-5.6% of the surface. Fenestrae developed in parallel with markedly reduced endothelial cell vesiculo-vacuolar organelles (VVOs). TA3/St tumors, which secreted more VPF/VEGF than MOT tumors, elicited mother vessels with unchanged VVOs and without fenestrae. In both tumors, a plasma protein tracer, ferritin, extravasated through VVOs and in MOT tumors ferritin also extravasated through fenestrae. Endothelial gaps were not observed in either tumor. Thus, not all VPF/VEGF-secreting tumors induce fenestrated endothelium. Also, VVOs provide an internal store of membrane that can be transferred to the endothelial cell surface to provide the substantial increase in plasma membrane necessary for mother vessel formation in MOT tumors. Such transfer was apparently unnecessary in TA3/St tumors in which extensive early endothelial cell division provided the increased plasma membrane necessary for forming mother vessels. (C) 2000 Academic Press.