Pleshkan Victor V, Zinovyeva Marina V, Antonova Dina V, Alekseenko Irina V
Gene Immunooncotherapy Group, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, 117997 Moscow, Russia.
National Research Center "Kurchatov Institute", 123182 Moscow, Russia.
Biomedicines. 2023 Jul 18;11(7):2017. doi: 10.3390/biomedicines11072017.
Fibroblast activation protein has a unique expression profile that manifests mainly in wounds and tumors, which anticipates it as an encouraging and selective target for anticancer therapy. However, research of the therapeutic potential of FAP is limited both by legal restraints when working in vivo and by the difficulty of obtaining standardized primary cultures of FAP-positive cancer-associated fibroblasts due to their high heterogeneity. We found that 3D spheroids of FAP-positive cell lines could serve as robust and convenient models of FAP expression, in contrast to monolayers. By exposing such spheroids to various factors and compounds, it is possible to study changes in FAP expression, which are easily detected by confocal microscopy. FAP expression increases under the influence of the TGFβ, does not depend on pH, and decreases during hypoxia and starvation. We believe that the proposed model could be used to organize large-scale high-throughput screening of drugs that target FAP expression.
成纤维细胞活化蛋白具有独特的表达模式，主要表现在伤口和肿瘤中，这使其有望成为抗癌治疗中一个令人鼓舞的选择性靶点。然而，FAP治疗潜力的研究受到体内研究时的法律限制，以及由于FAP阳性癌相关成纤维细胞高度异质性而难以获得标准化原代培养物的限制。我们发现，与单层细胞相比，FAP阳性细胞系的3D球体可作为FAP表达的强大且便捷的模型。通过将此类球体暴露于各种因子和化合物，可以研究FAP表达的变化，通过共聚焦显微镜很容易检测到这些变化。FAP表达在TGFβ的影响下增加，不依赖于pH值，在缺氧和饥饿期间降低。我们相信，所提出的模型可用于组织针对FAP表达的药物的大规模高通量筛选。
