Abstract 6769: Applications of a novel fibrous extracellular matrix for advanced in vitro cancer models

Abstract

Abstract Compared to traditional in vitro two-dimensional (2D) planar cell culture system, three-dimensional (3D) mammalian cell culture can better recapitulate physiological environments and the complexity of natural tissues, hence they are crucial in modern biomedical research. Extracellular matrices (ECM) play a key role in in vitro mammalian cell culture systems. The role of the ECM on in vitro 3D cell culture are: 1) to simulate an in vivo-like physiological environment, 2) support cell-cell and cell-ECM interactions, 3) promote cell adhesion, migration, and communication, 4) aid in tissue development, morphogenesis, differentiation, and functioning. Although basal membrane extracts (BME) are the most popular type of ECM supporting 3D modeling in vitro, they often have significant limitations including limited long-term stability, significant batch to batch heterogeneity, restricted cell movement, and relatively high cost for culturing many cancer cell lines. In this investigation, we employ a novel micro-fibrous scaffold that closely mimics natural ECM, providing porous and interconnected networks for 3D culturing of hepatic cells, lung cancer, breast cancer, pancreatic cancer. As revealed by optical and scanning electron microscopy, the scaffold promotes significant cell-to-cell and cell-to-matrix interactions. Moreover, we observed improved cell growth in 3D culture over longer periods than 2D culture systems for all cell types examined. We also evaluated the anticancer efficiency of different drugs including Lapatinib, Cisplatin, Docetaxel, Doxorubicin and observed that 2D cultured cells were more sensitive to drugs treatment in comparison to 3D. Furthermore, ECM was observed to support 3D growth and structure formation with cell pools of primary cells achieved from disassociated human tumors. Tumor organoids were able to form within seven days and ready for anticancer screening within 14 days. We achieved an 80% success rate in developing breast cancer organoids from patient tissues. Additionally, tissue granules were also able to be cultured under the same condition, which allowed us to investigate the invasion of cancer cells into tissue. The primary cells from human tumors formed cell clusters resembling the original tumor tissue's structure. In conclusion, the novel micro-fibrous scaffold, closely mimicking natural extracellular matrixes, promotes significant cell-to-cell and cell-to-matrix interactions, while also facilitating cell growth over extended periods providing a more physiologically relevant platform for evaluating drug responses for various cancer cell types, further showing the importance of 3D culture systems in cancer research. Citation Format: Navneet Kaur, Dazhi Yang, Jamel Ali. Applications of a novel fibrous extracellular matrix for advanced in vitro cancer models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6769.