膀胱肿瘤微环境模拟平台构建及实验-研究

《膀胱肿瘤微环境模拟平台构建及实验-研究》由会员上传分享，免费在线阅读，更多相关内容在教育资源-天天文库。

1、3.2.2膀胱肿瘤T24细胞网状结构形成·························································123.2.3巨噬细胞迁移·················································································123.3微环境模拟平台中间质细胞的活化·························································133.4微环境模拟平台中T24细胞对化疗药物的敏感性·············

2、··························144．讨论·································································································15结论······································································································17参考文献···············································

3、·················································18综述······································································································21参考文献································································································29攻读学位期间的研究成果··················

4、························································32致谢······································································································33学位论文独创性声明、学位论文知识产权权属声明·········································34万方数据引言引言:膀胱肿瘤是泌尿系统最常见的恶性肿瘤之一，具有较高死亡率，严重威胁人类健康。有关资料表明，世界范围内，

5、膀胱癌死亡率在所有恶性肿瘤疾病中排第11位。[1]肿瘤细胞学研究是探索肿瘤发生、发展、演进及预后的重要方法。目前，基于肿[2]瘤细胞学的研究多以单种细胞培养或二维细胞培养为主，以上体外培养条件下，细胞形态及生物学行为均有别于体内。微环境在肿瘤细胞的增值、进展及远处转移方面起着重要作用。相关研究表明，[3]肿瘤间质与肿瘤细胞共同决定了肿瘤组织的恶性表型。肿瘤微环境由肿瘤细胞、间质中的非瘤生细胞及胞外基质构成；间质中的非肿瘤细胞主要由内皮细胞、成纤维细胞、巨噬细胞及其他免疫细胞组成。肿瘤细胞与其微环境中非瘤生细胞间的相互作用可以调控肿瘤的血管增殖，钝化免疫系统攻击，逃避免疫

6、监视，使肿瘤不断[4,5]向周围组织侵袭转移。内皮细胞作为构成肿瘤微血管的最重要细胞，在肿瘤组织的氧气、营养物质的供给及生物因子运输中起着重要的作用。血管内皮细胞与肿瘤细胞的相互作用是肿瘤细胞穿越血管屏障的重要途径，在肿瘤的跨血管迁移过程中[6]不可或缺。近年来，代谢成为肿瘤研究的另一热点，相关研究表明，肿瘤微环境的物质代谢会导致乳酸生成及氧分压波动，该波动的酸性微环境可以募集与活化内[7]皮细胞，促进肿瘤相关血管的生成与演进。成纤维细胞作为肿瘤微环境中数量最多的非肿瘤细胞与肿瘤的生物学行为关系紧密。研究表明，肿瘤细胞产生的多种生物因子可促进成纤维细胞向肿瘤相关成纤维细

7、胞转化，如血小板源性生长因子（PDGF-α/β）、碱性成纤维细胞生长因子(bFGF)、白细胞介素（IL-1β）、γ干扰素（IFN-γ）、前列腺素E（PGE）等；同时，肿瘤相关成纤维细胞分泌的肝细胞生长因子（HGF）、CXC趋化因子14抗体（CXL14）、趋化因子配体7（CCL7）、基质[8]细胞衍生因子（SDF-1）等又可以影响肿瘤细胞的生物学行为。肿瘤微环境中存在的细胞活素可与多种细胞相互作用，成为重要的“结点”分子影响着肿瘤细胞的恶性表型。比如，肿瘤相关成纤维细胞可介导透明质酸酶在肿瘤微环境中高表达，而透明质酸酶可使肿瘤相关成纤维细胞