基于微流控芯片构建三维基质支架中的肿瘤细胞侵袭模型  

A novel cancer invasion model based on a microfluidic device in a 3-dimensional matrix

作　　者：宋振[1] 蔡绍皙[1] 陈斯佳[1] 晏小清[1] 孙炜[1] 卢斯媛[1] 

机构地区：[1]重庆大学生物工程学院,生物流变科学与技术教育部重点实验室,重庆400044

出　　处：《科学通报》2012年第23期2184-2191,共8页Chinese Science Bulletin

基　　金：国家自然科学基金(11172339);“211工程”三期建设(S-09104);重庆大学大型仪器设备开放基金资助

摘　　要：肿瘤细胞侵袭是一个复杂而高度协调的过程,传统的实验技术,如Boyden小室、Transwell小室法大多只能在二维(2D)尺度下研究肿瘤细胞侵袭,并不能反映体内的侵袭微环境以及监测侵袭过程.为得到更为真实可信的侵袭结果,在体外构建一种三维(3D)肿瘤细胞侵袭模型是十分必要的.本研究在微流控技术基础上自行设计和构建肿瘤细胞侵袭模型,该模型不仅能够模拟肿瘤细胞的侵袭3D微环境,而且能够监测肿瘤细胞与3D微环境的相互作用,以及全程监测生化因子对肿瘤细胞侵袭过程的动态影响.为评价该芯片用于研究肿瘤细胞侵袭机制的可行性和优越性,用该芯片模拟乳腺肿瘤细胞(MDA-MB-231)的3D微环境,并全程监测在细胞坏死因子(TNF-α)浓度梯度诱导下,MDA-MB-231侵袭的全过程.该模型实验结果表明,TNF-α能够诱导MDA-MB-231在3D基质胶中进行定向侵袭,并且发现侵袭到基质胶中的MDA-MB-231会形成具有侵袭突起的顶细胞,顶细胞和柄细胞首尾相连形成线状.该微流控芯片有望为研究肿瘤细胞的侵袭机制和开发抑制肿瘤细胞侵袭药物提供一个新的研究平台.Cancer-cell invasion is a complex and highly coordinated process. Traditional experimental methods involving Boyden and transwell chamber models are suitable for counting the numbers of cancer cells invading through the base membrane in 2-dimensional culture, but are unable to mimic the extracellular matrix or monitor the live process of cancer-cell invasion. To obtain a more authentic representation of cancer-cell invasion, we therefore created a novel in vitro invasion model. In contrast to traditional methods, this model was better able to simulate the extracellular matrix, track the process of cancer cell invasion, and observe the tumor cell-extracellular matrix interactions. We evaluated the potential of this microfluidic device for investigating the mechanism of cancer-cell invasion by mimicking the extracellular matrix of MDA-MB-231 cells and monitoring MDA-MB-231 cell invasion in a stable concentration gradient of tumor necrosis factor-a （TNF-a） in a 3-dimensional extracellular matrix. Our results showed that cancer cells responded to TNF-a stimulation by forming cellular protrusions and migrating towards high TNF-a concentrations. MDA-MB-231 cells connected with each other in a linear manner in the 3-dimensional extracellular matrix. These observations suggest that this microfluidic device represents a useful platform for elucidating the mechanisms of cancer invasion and for screening anti-invasion drugs for cancer therapy.

关 键 词：微流控芯片 3D 侵袭 肿瘤坏死因子 

分 类 号：R730.2[医药卫生—肿瘤]