MicroPET/SPECT/CT Imaging Laboratory, Centre for BioMedical Imaging (CIBM), University Hospitals and University of Geneva, 1211 Geneva 4, Switzerland.
Department of Thoracic and Endocrine Surgery, University Hospitals and University of Geneva, 1211 Geneva 4, Switzerland.
Int J Mol Sci. 2018 Jun 26;19(7):1881. doi: 10.3390/ijms19071881.
Malignant pleural mesothelioma (MPM) is a thoracic aggressive cancer caused by asbestos exposure, which is difficult to diagnose and treat. Here, we characterized an in vivo orthotopic xenograft model consisting of human mesothelioma cells (designed as H2052/484) derived from a pleural NCI-H2052 tumor injected in partially immunodeficient athymic mice. We assessed tumor formation and tumor-dependent patterns of inflammation. H2052/484 cells conserved their mesothelioma phenotype and most characteristics from the parental NCI-H2052 cells. After intra-thoracic injection of H2052/484 cells, thoracic tumors developed in nearly all mice (86%) within 14 days, faster than from parental NCI-H2052 cells. When the mice were euthanized, the pleural lavage fluid was examined for immune cell profiles. The pleural immune cell population increased with tumor development. Interestingly, the proportion of myeloid-derived suppressor cell and macrophage (especially CD206⁺ M2 macrophages) populations increased in the pleural fluid of mice with large mesothelioma development, as previously observed in immunocompetent mice. This reliable orthotopic model recapitulates human mesothelioma and may be used for the study of new treatment strategies.
恶性胸膜间皮瘤（MPM）是一种由石棉暴露引起的胸部侵袭性癌症，其诊断和治疗都很困难。在这里，我们描述了一个由源自胸膜 NCI-H2052 肿瘤的人胸膜间皮瘤细胞（设计为 H2052/484）在部分免疫缺陷的无胸腺小鼠中注射而建立的体内原位异种移植模型。我们评估了肿瘤形成和肿瘤依赖性炎症模式。H2052/484 细胞保留了其间皮瘤表型和来自亲本 NCI-H2052 细胞的大多数特征。在胸内注射 H2052/484 细胞后，14 天内几乎所有小鼠（86%）都出现了胸腔内肿瘤，比亲本 NCI-H2052 细胞更快。当小鼠被安乐死时，检查胸腔灌洗液中的免疫细胞谱。随着肿瘤的发展，胸腔免疫细胞群增加。有趣的是，在间皮瘤发育较大的小鼠胸腔灌洗液中，髓源抑制细胞和巨噬细胞（特别是 CD206+M2 巨噬细胞）的比例增加，这与在免疫功能正常的小鼠中观察到的情况相同。这种可靠的原位模型重现了人类间皮瘤，可用于研究新的治疗策略。
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