基于微流控芯片的胰腺癌细胞可变形性与侵袭能力相关性研究

Pancreatic cancer is a highly malignant tumor. Invasion and metastasis is its leading cause of death. As one of the core issues in the metastatic mechanism of pancreatic cancer, the correlation between the deformability and invasive potential of pancreatic cancer cells is of great significance for a deep understanding of the metastatic mechanism of pancreatic cancer, as well as finding new targets genes for blocking the metastasis of pancreatic cancer. However, the correlation between the deformability and invasive potential of pancreatic cancer cells is still not clear. Accurately characterizing tumor cells invasion under complex and variable tumor microenvironments remains challenging. This project intends to use microfluidics as the core technology. The microfluidic chips are employed to simulate the tumor microenvironment of pancreatic cancer, at the same time to characterize the invasive potential of pancreatic cancer cells. Then a high-throughput microchannel chip is used to characterize pancreatic cancer cells’deformability. The correlative analysis will be used to obtain the correlation coefficient of pancreatic cancer cell deformability and invasion potential. The factors influencing this correlation will be analyzed to establish a correlation mathematical model. Then we will explore the molecular mechanism of pancreatic cancer cell deformability and invasive potential correlation. We will screen genes that have a significant effect on the deformability of pancreatic cancer cells, and explore the possibility that the target gene becomes a new target for blocking pancreatic cancer metastasis. The implementation of this project can provide a reference for studying the mechanism of pancreatic cancer metastasis.

胰腺癌是恶性程度极高的肿瘤，侵袭转移是其主要的致死原因。作为胰腺癌转移机制的核心问题之一，胰腺癌细胞可变形性与侵袭能力相关性研究对于深入理解胰腺癌转移机制，寻找阻断胰腺癌转移的新靶点有重要意义。但是目前胰腺癌细胞可变形性与侵袭能力相关性并不明确，在复杂多变的肿瘤微环境下精确表征肿瘤细胞侵袭能力仍然极具挑战。本项目拟以微流控为核心技术，利用微流控芯片模拟胰腺癌肿瘤微环境，表征肿瘤微环境下胰腺癌细胞侵袭能力，同时基于高通量微沟道芯片表征胰腺癌细胞可变形性；通过相关性分析获得胰腺癌细胞可变形性-侵袭能力相关系数，分析影响该相关性的因素，建立相关性数学模型；探索胰腺癌细胞变形性与侵袭能力相关性的分子机制，筛选对胰腺癌细胞可变形性影响较显著的基因，探讨目标基因成为阻断胰腺癌转移新靶点的可能性。本项目的实施，可为研究胰腺癌转移机制提供借鉴。

胰腺癌是恶性程度极高的肿瘤，侵袭转移是其主要的致死原因。作为胰腺癌转移机制的核心问题之一，胰腺癌细胞可变形性与侵袭能力相关性研究对于深入理解胰腺癌转移机制，寻找阻断胰腺癌转移的新靶点有重要意义。腺癌细胞可变形性与侵袭能力相关性并不明确，在复杂多变的肿瘤微环境下精确表征肿瘤细胞侵袭能力仍然极具挑战。在项目支持下，研究团队研究针对胰腺癌转移的关键问题——胰腺癌细胞可变形性与侵袭能力相关性开展深入研究。团队利用COMSOL软件仿真获取微流控芯片微沟道中流体场和压力场分布，计算单细胞通过ECM、血管中的微小缝隙过程，以及在此过程的受力情况；团队利用微流控技术制备了多层器官芯片模拟肿瘤微环境中物理因素以及趋化因子等，模拟了血管等关键环境因素，同时模拟了在该微环境下加药对于肿瘤进展的影响；团队开发出新的基于细胞高速图像处理的神经网络，用于肿瘤细胞识别方法以及细胞可变形性表征方法，同时与传统电学方法结果进行对照，获得更准确的细胞可变形性数据。在此基础上，获取胰腺癌细胞可变形性与侵袭能力相关系数及基本特征，建立相关性模型。获得了可变形性较高的PANC细胞更具有侵袭性的证据，证明了PANC细胞的细胞硬度和侵袭潜能之间的密切联系。本项目执行期内，组织国际会议IEEE ISNE 2019一次；参加国际会议6人次，参加国内会议12人次； 培养博士研究生3名，硕士研究生10名；此外，申请人以通信作者身份发表SCI论文16篇，其中包括《Small》、《Biosensor & Bioelectronics》、《Lab on a Chip》等国际微流控领域权威中科院一区期刊论文8篇，同时，申请发明专利5项。所有指标均超额完成。