Prado-López Sonia, Foroughipour Massih, Becker Klaus, Foroughipour Seyed Meraaj, Weber Lukas, Wanzenboeck Heinz, Sarem Nika, Saghafi Saiedeh
Research Unit of Nanoelectronic Devices, Institute of Solid State Electronics, Faculty of Electrical Engineering and Information Technology, TU Wien, Vienna, Austria.
Meso-Aspheric Optics & LSFM Group, Institute of Solid State Electronics, Faculty of Electrical Engineering and Information Technology, TU Wien, Vienna, Austria.
BJC Rep. 2025 Jun 18;3(1):45. doi: 10.1038/s44276-025-00144-3.
Three dimensional tumoral models are essential to study cancer biology as they better mimic the complexity of the tumoral masses in vivo. However, to study cancer 3D models' dynamics new technological approaches are required. Most of the deaths related to cancer are caused by metastasis but still many of the metastatic driving processes remain unknown. A fundamental player in the metastatic process is the cytoskeleton. The polymerization of actin monomers in filaments, known as F-actin, is crucial for cell motility. Also, it can be used to detect necrosis, since F-actin is exposed on necrotic cells due to the loss of the cell membrane's integrity. To date, studies of actin dynamics in cancer cells have primarily relied on simplistic 2D models and fluorescence microscopy.
In this paper, we propose combining light sheet fluorescence microscopy (LSFM) with colorectal cancer (CRC) and non-small cell lung carcinoma (NSCLC) spheroids to study F-actin distribution and exposition with minimal distortions.
We identified 6 different areas of F-actin intensity that could be correlated with the proliferative, senescence and necrotic zones previously described in cancer spheroid models in vitro.
Our findings proved the power of the proposed LS meso aspheric optics approach to visualize and quantify F-actin in 3D cancer models with a high level of detail. Importantly, our findings also facilitate the assessment of the necrotic area's extent, clearing the path for improved anti-metastatic treatments and more accurate patient prognosis evaluation.
三维肿瘤模型对于研究癌症生物学至关重要，因为它们能更好地模拟体内肿瘤块的复杂性。然而，要研究癌症三维模型的动态变化，需要新的技术方法。大多数与癌症相关的死亡是由转移引起的，但许多转移驱动过程仍不清楚。转移过程中的一个关键因素是细胞骨架。肌动蛋白单体聚合成细丝，即F-肌动蛋白，对细胞运动至关重要。此外，它还可用于检测坏死，因为由于细胞膜完整性丧失，F-肌动蛋白会暴露在坏死细胞上。迄今为止，对癌细胞中肌动蛋白动力学的研究主要依赖于简单的二维模型和荧光显微镜。
在本文中，我们建议将光片荧光显微镜（LSFM）与结直肠癌（CRC）和非小细胞肺癌（NSCLC）球体相结合，以研究F-肌动蛋白的分布和暴露情况，且失真最小。
我们确定了6个不同的F-肌动蛋白强度区域，这些区域可能与先前在体外癌症球体模型中描述的增殖、衰老和坏死区域相关。
我们的研究结果证明了所提出的LS中球差光学方法在以高细节水平可视化和量化三维癌症模型中的F-肌动蛋白方面的能力。重要的是，我们的研究结果还有助于评估坏死区域的范围，为改进抗转移治疗和更准确的患者预后评估扫清道路。
