Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Seoul National University, Seoul 08826, Korea.
Laboratory of Veterinary Internal Medicine, College of Veterinary Medicine, Jeju National University, Jeju 63243, Korea.
J Vet Sci. 2021 May;22(3):e25. doi: 10.4142/jvs.2021.22.e25. Epub 2021 Mar 5.
Malignant 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.
In 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).
A 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.
TCs cocultured with SCs were found to have significantly upregulated multidrug resistance genes, such as , , and , 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.
SCs 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.
恶性淋巴瘤是犬最常见的血液恶性肿瘤，尽管初始治疗积极，但仍经常复发。为了使这些犬复发性淋巴瘤的治疗有效，选择个性化和敏感的抗癌药物非常重要。为了为药物开发和个性化癌症治疗提供可靠的工具，保持原始肿瘤的关键特征至关重要。
本研究建立了混合肿瘤/基质球体模型，并研究了犬淋巴瘤细胞系（GL-1）与犬淋巴结（LN）来源的基质细胞（SCs）之间的关联。
使用超低附着板创建由 GL-1 细胞和 LN 来源的 SC 组成的混合球体模型。使用共培养系统研究 SC 与 TC 之间的关系。
与 TC 单培养相比，与 SC 共培养的 TC 中发现多药耐药基因，如 、 、 和 ，显著上调。此外，结果表明，与 SC 共培养可降低阿霉素诱导的 GL-1 细胞凋亡和 G2/M 细胞周期阻滞。
SCs 在 TC 中上调多药耐药基因，并在存在抗癌药物时影响 TC 的凋亡和细胞周期。本研究表明，了解肿瘤微环境与 TC 之间的相互作用对于设计个性化药物的实验方法和预测药物的效果至关重要。
