Abstract P2-21-11: A high content imaging and analysis approach to screen compounds for novel drug targets in 3D breast cancer co-culture model

Cancer Research(2023)

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摘要
Abstract The desired effect of cancer therapeutics can only be conceived when applied to complex multicellular structures with different cell types and extracellular matrix (ECM) in three-dimensional (3D) space. Therefore, 3D cell culture systems have become very popular in drug screening and discovery. There is an immense demand for highly efficient and easy methods to produce 3D spheroids in any cell format. However, heterogeneity in size, extended cultivation times, and reproducibility for high throughput assays are limiting factors in the generation of spheroids. Recently we have established a naturally transformed breast cancer cell line, KAIMRC1 (1), from ductal breast carcinoma. We have developed a novel and easy method to produce spheroids (2) from KAIMRC1 cells in vitro, which can be used as a 3D model to study proliferation, differentiation, metabolism, cell death, and drug response of cells in the tumor microenvironment. We developed an in-vitro high content imaging (HCI) based cellular assay using commercially available compound panels to perform initial drug screening in the KAIMRC1 spheroids model. Our approach allows rapid screening of a panel of drugs to assess inhibitory effects on the growth of tumor cells in 3D cultures. To mimic the actual in-vivo tumor microenvironment, we are now developing an HCI-based assay utilizing 3D KAIMRC1 spheroids co-cultured with patient-derived fibroblast cells. 1. Ali, Rizwan, et al. “Isolation and Characterization of a New Naturally Immortalized Human Breast Carcinoma Cell Line, KAIMRC1.” BMC Cancer 17 (2017) 2. Rizwan Ali et al., (2021) New Born Calf Serum (NBCS) can induce spheroid formation in breast cancer KAIMRC1 cell line. Front. Mol. Biosci. DOI: 10.3389/fmolb.2021.769030 Citation Format: Rizwan Ali, Sarah Huwaizi, Arwa Alsubait, Mohamed Boudjelal. A high content imaging and analysis approach to screen compounds for novel drug targets in 3D breast cancer co-culture model [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-21-11.
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关键词
novel drug targets,breast cancer,compounds,high content imaging,co-culture
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