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人脑胶质瘤新生血管的细胞来源与血液流通功能的初步评价
  • ISSN号:0253-3766
  • 期刊名称:《中华肿瘤杂志》
  • 时间:0
  • 分类:R73-3[医药卫生—肿瘤;医药卫生—临床医学]
  • 作者机构:[1]上海交通大学医学院苏州九龙医院神经外科,215021, [2]苏州大学附属第二医院神经外科
  • 相关基金:国家重点基础研究发展计划(973)项目(2010CB529400);国家自然科学基金(30872654、81071766);江苏省自然科学基金(BK2008173、BK2010227);苏州市科技发展计划项目(YJS0950)
中文摘要:

目的探讨胶质瘤中部分新生血管是否源于胶质瘤干细胞转分化,并初步评价其血液运输功能。方法将SHG44人脑胶质瘤细胞系接种于30只NC裸小鼠皮下和20只NC裸小鼠脑内尾状核,将SU-2细胞接种于12只表达绿色荧光蛋白的NC/C57BL/6J-绿色荧光蛋白裸小鼠的尾状核内。取移植瘤组织,石蜡切片后,分别进行CD34-PAS双染及CD31、CD34、CD133、胶质纤维酸性蛋白(GFAP)、人类白细胞抗原(Ki67)、HLA免疫组化染色,并结合HLA免疫荧光共聚焦显微成像对移植瘤血管进行分类,对肿瘤血管起源细胞进行鉴定。每组取3只荷瘤鼠,以活性炭颗粒混悬液行心脏灌注,对移植瘤切片进行相应的免疫组化染色,并在光镜下观察炭颗粒在肿瘤血管中的分布。结果裸小鼠移植瘤中,同时存在CD34一PAS双阳性的内皮细胞依赖型血管、CD34-PAS^+的血管生成拟态和由肿瘤细胞与CD34^+细胞嵌合而成的马赛克血管,炭颗粒随机分布在这些血管腔内。在人脑胶质瘤干细胞移植瘤中,CD31^+细胞依附于血管壁腔侧面;CD34^+细胞亦沿血管分布,但在形态上介于肿瘤细胞与内皮细胞之间;在血管壁上可见HLA^+和人Ki67^+细胞,提示构成血管壁的这些细胞来自人源细胞。HLA免疫荧光共聚焦显微成像可见,移植瘤中的血管以表达HLA(红色)的人源肿瘤细胞为主,兼有表达GFP(绿色)的宿主细胞,或人鼠融合细胞。结论在移植性人脑胶质瘤组织中存在具有血液运输功能的内皮细胞依赖型血管、血管生成拟态和马赛克血管3类血管,人脑胶质瘤干祖细胞有通过分化和转分化机制自主形成后两类肿瘤血管的潜能。

英文摘要:

Objective The finding of vasculogenic mimicry (VM) in many solid tumors indicates that tumor cells themselves could participate in the construction of tumor vessels. However the origin of these cells is still not fully elucidated, and whether these vessels have the ability of blood-supply is still unclear. Preliminary studies were performed to investigate whether part of tumor neovascularity is derived from tumor stem cells (TSCs) and whether TSCs-derived vessels are functional. Methods Transplanted glioma tissues obtained from subcutaneous and orthotopic transplantation nude mouse models were processed into paraffin sections. In order to identify the cell origin and types of tumor vessels, sections were stained with CD31, CD34, CD133, GFAP, Ki67 and HLA, respectively. CD34-PAS staining was performed as well. A part of tumor-bearing mice were perfused with activated carbon through the systemic circulation and the distribution of activated carbon was observed. Results CD34-PAS staining showed that endothelium-dependent vessels ( CD34 ^+ , PAS ^+ ), VM vessels ( CD34-, PAS ^+ ), and the MVs ( CD34 ^+ , PAS- ) could be seen in the transplantated tumors. Activated carbon particles were observed in all three types of vessels. CD31 ^+ cells adherent to the luminal surface of vessel wall. CD34 ^+ cells distributed along the vessels as well, but morphologically were more like a transition type between tumor cells and endothelial cells. Human specific Ki67 and HLA positive cells could be seen in the tumor vessels indicating that these vessels were derived from human tumor cells. Moreover, cells of tumor vessels were proved to be constructed by human tumor cells mainly and fusion cells of host cells and tumor cells under confocal microscope. Conclusions Three types of blood supply sources including endothelium-dependent vessels, vasculogenic mimicry (VMs) and mosaic vessels (MVs) exist in transplantation tumors of human glioma. Glioma stem and progenitor cells (GSCPs) have the po

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期刊信息
  • 《中华肿瘤杂志》
  • 北大核心期刊(2011版)
  • 主管单位:中国科协
  • 主办单位:中华医学会
  • 主编:
  • 地址:北京市朝阳区潘家园17号
  • 邮编:100021
  • 邮箱:zhoonghuazhongliu@163@com
  • 电话:010-67788231
  • 国际标准刊号:ISSN:0253-3766
  • 国内统一刊号:ISSN:11-2152/R
  • 邮发代号:2-47
  • 获奖情况:
  • 科协优秀期刊二等奖,首届国家期刊奖提名奖,中国期刊方阵双奖期刊
  • 国内外数据库收录:
  • 美国化学文摘(网络版),荷兰文摘与引文数据库,荷兰医学文摘,美国生物医学检索系统,美国生物科学数据库,日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2004版),中国北大核心期刊(2008版),中国北大核心期刊(2011版),中国北大核心期刊(2014版),中国北大核心期刊(2000版)
  • 被引量:43252