构建合适的肿瘤细胞侵袭模型、开发肿瘤细胞侵袭的定量监测方法一直是癌症研究的热点。构建了厚度超过1 mm的三维肿瘤体外侵袭模型,利用搭建的超宽带谱域光学相干层析成像系统,检测了细胞的迁移和侵袭动态,从细胞迁移距离变化和基质材料分解两方面来表征肿瘤细胞的体外侵袭过程;通过光学相干层析成像散射界面的峰值变化来定量检测肿瘤细胞的迁移距离,结合三维图像量化基质材料的表面曲度、厚度、整体体积变化来表征肿瘤细胞侵袭过程的基质材料分解与变形信息。结果表明:光学相干层析成像技术检测到的肿瘤细胞侵袭引起的细胞团簇位置变化、基质材料形态改变与苏木精-伊红染色切片、激光共聚焦结果相匹配,验证了光学相干层析成像技术检测肿瘤细胞侵袭的可行性;通过设计不同营养梯度、不同pH微环境下的三维肿瘤模型,利用搭建的光学相干层析成像系统,准确地量化了不同时间、不同体外微环境下肿瘤细胞的迁移距离、基质材料表面曲度、厚度和整体体积变化。与苏木精-伊红染色、激光共聚焦方法相比,所提方法可以连续监测肿瘤细胞的侵袭过程,更全面地反映肿瘤细胞迁移和侵袭的机理。

Cancer research has increasingly focused on developing appropriate tumor cell invasion models and developing a quantitative method to monitor tumor cell invasion. In this study, a three-dimensional tumor invasive model with >1 mm thickness is constructed. An ultra-wideband spectral domain optical coherence tomography system is used to detect cell migration and invasion dynamics, and the in vitro invasion process of tumor cells is characterized by the change of cell migration distance and matrix material decomposition. The quantitative detection of tumor cell migration distance based on peak change of the optical coherence tomography scattering interface is combined with three-dimensional images to quantify the matrix surface curvature, thickness, and overall volume change, thereby realizing the characterization of the matrix material decomposition and deformation information during tumor cell invasion. The changes of cell cluster positions caused by tumor cell invasion and morphological changes of matrix materials are matched with hematoxylin-eosin staining sections and laser confocal results, which verifies the feasibility of optical coherence tomography for detecting tumor-cell invasion. Three-dimensional tumor models under different nutrient gradients and different pH microenvironments are utilized. The established optical coherence tomography system accurately quantifies the migration distance of tumor cells and surface curvature and overall volume change of matrix materials at different time and in vitro microenvironments. Compared with hematoxylin-eosin staining and the laser confocal imaging method, the proposed optical coherence tomography-based method enables the continuous monitoring of the invasion process of tumor cells, thereby providing a more comprehensive view of tumor-cell migration and invasion mechanisms.