3D-culture models as drug-testing platforms in canine lymphoma and their cross talk with lymph node-derived stromal cells |
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| Authors: | Ju-Hyun An Woo-Jin Song Qiang Li Dong-Ha Bhang Hwa-Young Youn |
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| Institution: | 1.Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.;2.Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Jeju National University, Jeju 63243, Korea.;3.Department of Veterinary Medicine, College of Agriculture, Yanbian University, Yanji 133000, China.;4.Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 16419, Korea. |
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| Abstract: | BackgroundMalignant lymphoma is the most common hematopoietic malignancy in dogs, and relapse is frequently seen despite aggressive initial treatment. In order for the treatment of these recurrent lymphomas in dogs to be effective, it is important to choose a personalized and sensitive anticancer agent. To provide a reliable tool for drug development and for personalized cancer therapy, it is critical to maintain key characteristics of the original tumor.ObjectivesIn this study, we established a model of hybrid tumor/stromal spheroids and investigated the association between canine lymphoma cell line (GL-1) and canine lymph node (LN)-derived stromal cells (SCs).MethodsA hybrid spheroid model consisting of GL-1 cells and LN-derived SC was created using ultra low attachment plate. The relationship between SCs and tumor cells (TCs) was investigated using a coculture system.ResultsTCs cocultured with SCs were found to have significantly upregulated multidrug resistance genes, such as P-qp, MRP1, and BCRP, compared with TC monocultures. Additionally, it was revealed that coculture with SCs reduced doxorubicin-induced apoptosis and G2/M cell cycle arrest of GL-1 cells.ConclusionsSCs upregulated multidrug resistance genes in TCs and influenced apoptosis and the cell cycle of TCs in the presence of anticancer drugs. This study revealed that understanding the interaction between the tumor microenvironment and TCs is essential in designing experimental approaches to personalized medicine and to predict the effect of drugs. |
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| Keywords: | Canine lymphoma lymph node-derived stromal cell drug resistance personalized cancer therapy tumor microenvironment |
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