Establishment of a Small-cell Lung Cancer (SCLC) Mouse Model Using Enhanced Cancer Stem Cell–functioning 3D SCLC Spheroids

Abstract Despite its low incidence rate, small-cell lung cancer (SCLC), which accounts for approximately 10–15% of all lung cancers, is concerningly characterized by its rapid progression, strong metastatic potential, and high fatality rate. Therefore, an effective predictive model for SCLC treatment is imperative for early intervention. In this study, we aimed to enhance the cancer stem cell (CSC) capabilities of SCLC through a three-dimensional (3D) culturing approach and to evaluate its potential as a predictive model for therapeutic response in SCLC by transplanting the spheroids into mice. To achieve uniform and scalable production of 3D SCLC spheroids, the SpheroFILM culture platform was employed, and the expression of CSC markers was verified at the gene and protein levels within the spheroids cultured onboard. Moreover, spheroids were transplanted into mice to confirm gene and protein expression of CSC markers, tumor-formation capacity, proliferation ability, and invasion potential through histological staining. Based on our results, the transplantation of enhanced CSC–functioning 3D SCLC cell lines into mice led to a significant increase in tumor-formation capacity along with elevated expression of CSC markers. Thus, the results collectively suggest that the augmentation of CSC properties in 3D cultured cell lines, when transplanted into animal models, reduces necrosis and enhances tumor formation, proliferation, and invasion.