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Macrophage induces anti-cancer drug resistance in canine mammary gland tumor spheroid
Scientific Reports ( IF 3.8 ) Pub Date : 2023-06-27 , DOI: 10.1038/s41598-023-37311-w
Ga-Hyun Lim 1 , Ju-Hyun An 2 , Su-Min Park 1 , Ga-Hee Youn 1 , Ye-In Oh 3 , Kyoung-Won Seo 1 , Hwa-Young Youn 1
Affiliation  

Tumor-associated macrophages (TAMs) play an important role in the tumor microenvironment by producing cytokines and growth factors. Furthermore, TAMs play multifunctional roles in tumor progression, immune regulation, metastasis, angiogenesis, and chemoresistance. Hypoxia in the tumor microenvironment induces tumor-supporting transformation of TAMs, which enhances tumor malignancy through developing anti-cancer resistance, for example. In this study, a hybrid spheroid model of canine mammary gland tumor (MGT) cell lines (CIPp and CIPm) and canine macrophages (DH82) was established. The effects of hypoxia induced by the spheroid culture system on the anti-cancer drug resistance of canine MGT cells were investigated. A hybrid spheroid was created using an ultralow-adhesion plate. The interactions between canine MGT cells and DH82 were investigated using a co-culture method. When co-cultured with DH82, cell viability and expression levels of tumor growth factors and multi-drug resistance genes were increased in canine MGT cells under doxorubicin. Additionally, doxorubicin-induced apoptosis and G2/M cell cycle arrest were attenuated in canine MGT cells co-cultured with DH82. In conclusion, the hybrid spheroid model established in this study reflects the hypoxic TME, allowing DH82 to induce anti-cancer drug resistance in canine MGT cells.



中文翻译:

巨噬细胞诱导犬乳腺肿瘤球体产生抗癌药物耐药性

肿瘤相关巨噬细胞(TAM)通过产生细胞因子和生长因子在肿瘤微环境中发挥重要作用。此外,TAM 在肿瘤进展、免疫调节、转移、血管生成和化疗耐药中发挥多功能作用。例如,肿瘤微环境中的缺氧会诱导 TAM 的肿瘤支持性转化,从而通过产生抗癌耐药性来增强肿瘤的恶性程度。在本研究中,建立了犬乳腺肿瘤(MGT)细胞系(CIPp和CIPm)和犬巨噬细胞(DH82)的混合球体模型。研究球体培养系统诱导的缺氧对犬MGT细胞抗癌耐药性的影响。使用超低粘附力板创建混合球​​体。使用共培养方法研究了犬 MGT 细胞和 DH82 之间的相互作用。当与 DH82 共培养时,在多柔比星作用下,犬 MGT 细胞的细胞活力以及肿瘤生长因子和多药耐药基因的表达水平增加。此外,在与 DH82 共培养的犬 MGT 细胞中,阿霉素诱导的细胞凋亡和 G2/M 细胞周期停滞被减弱。总之,本研究建立的混合球体模型反映了缺氧TME,使DH82能够诱导犬MGT细胞产生抗癌耐药性。在与 DH82 共培养的犬 MGT 细胞中,阿霉素诱导的细胞凋亡和 G2/M 细胞周期停滞减弱。总之,本研究建立的混合球体模型反映了缺氧TME,使DH82能够诱导犬MGT细胞产生抗癌耐药性。在与 DH82 共培养的犬 MGT 细胞中,阿霉素诱导的细胞凋亡和 G2/M 细胞周期停滞减弱。总之,本研究建立的混合球体模型反映了缺氧TME,使DH82能够诱导犬MGT细胞产生抗癌耐药性。

更新日期:2023-06-29
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