Shindyapin Vadim V, Gubernatorova Ekaterina O, Gorshkova Ekaterina A, Chicherina Nelya R, Sysonov Fedor A, Yakovleva Anastasia S, Bogdanova Daria A, Demidov Oleg N, Samsonova Mariya V, Baklaushev Vladimir P, Yusubalieva Gaukhar M, Drutskaya Marina S
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia.
Department of Immunobiology and Biomedicine, Scientific Center of Genetics and Life Sciences, Sirius University of Science and Technology, Federal Territory Sirius, 354340 Krasnodar Krai, Russia.
Cells. 2024 Dec 23;13(24):2135. doi: 10.3390/cells13242135.
Malignant pleural mesothelioma is a neoplasm that is often detected late due to nonspecific symptoms. This study utilized NSG-SGM3 mice to examine interactions between a human-derived mesothelioma reporter cell line (MZT-Luc2-mCherry) and the host's myeloid compartment. Tumor growth was assessed using optical tomography, while cytokine/chemokine production was analyzed via multiplex assay. Histological and immunohistochemical analyses validated the epithelioid mesothelioma phenotype. In vitro mesothelioma cells secreted factors associated with myeloid cell chemoattraction and functions supporting the previously reported myeloid-biased secretory phenotype. In line with this, post-engraftment analysis revealed increased neutrophil-like Ly6G+ populations and decreased Ly6C+ inflammatory monocytes in the blood of tumor-bearing mice. Significant Ly6G+ cell infiltration was observed in the tumor, while CD11b+ myeloid cells were localized primarily in the tumor periphery. Tumor lysates showed increased levels of neutrophil chemoattractants and G-CSF, suggesting a previously not reported role of neutrophils in mesothelioma progression. This novel model provides a platform for studying mesothelioma-host interactions, focusing on the myeloid compartment. It may also serve as a tool to facilitate the development of new therapeutic strategies targeting myeloid cell-mediated mechanisms in mesothelioma.
恶性胸膜间皮瘤是一种由于症状不特异而常被晚期检测到的肿瘤。本研究利用NSG - SGM3小鼠来研究人源间皮瘤报告细胞系（MZT - Luc2 - mCherry）与宿主髓系区室之间的相互作用。使用光学断层扫描评估肿瘤生长，同时通过多重分析检测细胞因子/趋化因子的产生。组织学和免疫组织化学分析验证了上皮样间皮瘤表型。体外实验中，间皮瘤细胞分泌与髓系细胞趋化和功能相关的因子，支持先前报道的髓系偏向性分泌表型。与此一致，移植后分析显示荷瘤小鼠血液中嗜中性粒细胞样Ly6G +群体增加，Ly6C +炎性单核细胞减少。在肿瘤中观察到显著的Ly6G +细胞浸润，而CD11b +髓系细胞主要定位于肿瘤周边。肿瘤裂解物显示嗜中性粒细胞趋化因子和G - CSF水平升高，提示嗜中性粒细胞在间皮瘤进展中具有先前未报道的作用。这个新模型为研究间皮瘤与宿主的相互作用提供了一个平台，重点关注髓系区室。它也可作为一种工具，促进针对间皮瘤中髓系细胞介导机制的新治疗策略的开发。
