Cadena Melissa, DeLuna Frank, Baryeh Kwaku, Sun Lu-Zhe, Ye Jing Yong
Department of Biomedical Engineering, The University of Texas at San Antonio, 1 UTSA Circle, San Antonio, TX, 78249, USA.
Department of Cell Systems & Anatomy, The University of Texas Health at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229, USA.
Proc SPIE Int Soc Opt Eng. 2020 Feb;11251. doi: 10.1117/12.2544113. Epub 2020 Feb 20.
During prostate cancer progression, cancerous epithelial cells can undergo epithelial-mesenchymal transition (EMT). EMT is a crucial mechanism for the invasion and metastasis of epithelial tumors characterized by the loss of cell-cell adhesion and increased cell mobility. It is associated with biochemical changes such as epithelial cell markers E-cadherin and occludins being down-regulated, and mesenchymal markers vimentin and N-cadherin being upregulated. These changes in protein expression, specifically in the cell membrane, may be monitored via biophysical principles, such as changes in the refractive index (RI) of the cell membrane. In our previous research, we demonstrated the feasibility of using cellular RI as a unique contrast parameter to accomplish label-free detection of prostate cancer cells. In this paper, we report the use of our Photonic-Crystal biosensor in a Total-Internal-Reflection (PC-TIR) configuration to construct a label-free biosensing system, which allows for ultra-sensitive quantification of the changes in cellular RI due to EMT. We induced prostate cancer cells to undergo EMT by exposing these cells to soluble Transforming Growth Factor Beta 1 (TGF-β1). The biophysical characteristics of the cellular RI were quantified extensively in comparison to non-induced cancer cells. Our study shows promising clinical potential in utilizing the PC-TIR biosensing system not only to detect prostate cancer cells, but also to evaluate changes in prostate cancer cells due to EMT.
在前列腺癌进展过程中，癌上皮细胞可发生上皮-间质转化（EMT）。EMT是上皮肿瘤侵袭和转移的关键机制，其特征是细胞间黏附丧失和细胞迁移增加。它与生化变化相关，如上皮细胞标志物E-钙黏蛋白和闭合蛋白下调，以及间质标志物波形蛋白和N-钙黏蛋白上调。这些蛋白质表达的变化，特别是细胞膜上的变化，可以通过生物物理原理进行监测，如细胞膜折射率（RI）的变化。在我们之前的研究中，我们证明了使用细胞RI作为独特的对比参数来实现前列腺癌细胞无标记检测的可行性。在本文中，我们报告了使用处于全内反射（PC-TIR）配置的光子晶体生物传感器构建无标记生物传感系统，该系统能够对由于EMT导致的细胞RI变化进行超灵敏定量。我们通过将这些细胞暴露于可溶性转化生长因子β1（TGF-β1）来诱导前列腺癌细胞发生EMT。与未诱导的癌细胞相比，对细胞RI的生物物理特性进行了广泛的定量分析。我们的研究表明，利用PC-TIR生物传感系统不仅可以检测前列腺癌细胞，还可以评估由于EMT导致的前列腺癌细胞变化，具有广阔的临床应用潜力。
