Chai Ranran, Zheng Kewei, Xu Ting, Wang Hui, Cheng Xiaobo, Lu Chong, Kang Yu
Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China.
Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China.
Biomedicines. 2025 Apr 23;13(5):1021. doi: 10.3390/biomedicines13051021.
Tumor-associated macrophages (TAMs) are prevalent in advanced ovarian cancer tissues and ascites, significantly influencing disease prognosis. However, the mechanisms driving TAM polarization and their tumor-promoting effects remain poorly understood. : The subcellular distribution of SNX10 in ovarian cancer tissues was analyzed using single-cell datasets (GSE147082, GSE58937). The Kaplan-Meier Plotter and GEPIA2 databases were used to evaluate SNX10's prognostic relevance. Lentivirus-mediated overexpression in THP-1 cells was employed in tumor cell-macrophage co-culture experiments. Transwell assays and flow cytometry assessed SNX10's effects on ovarian cancer cell metastasis and cisplatin-induced apoptosis. RNA sequencing, Western blotting, lysosomal pH detection, lipid droplet staining, and RT-qPCR were performed to explore SNX10's molecular mechanisms in TAM polarization and immune modulation. : SNX10 was specifically expressed in TAMs, promoting their polarization into the M2 phenotype. This enhanced the migration and invasion of ovarian cancer cell lines A2780 and A2780/CP70 while reducing cisplatin-induced apoptosis. SNX10 decreased lipid droplet content, downregulated p-mTOR1, and impaired lysosomal function in TAMs. Additionally, SNX10 differentially modulated mRNA expression in platinum-sensitive and platinum-resistant ovarian cancer cells. : SNX10 regulates the mTOR1/lysosome pathway in TAMs, influencing lipid metabolism and indirectly modulating ovarian cancer cell metastasis. It also alters mRNA expression, suggesting a role in shaping the tumor immune microenvironment.
肿瘤相关巨噬细胞(TAM)在晚期卵巢癌组织和腹水中普遍存在,对疾病预后有显著影响。然而,驱动TAM极化的机制及其促肿瘤作用仍知之甚少。:利用单细胞数据集(GSE147082、GSE58937)分析了卵巢癌组织中SNX10的亚细胞分布。使用Kaplan-Meier Plotter和GEPIA2数据库评估SNX10的预后相关性。在肿瘤细胞-巨噬细胞共培养实验中采用慢病毒介导的THP-1细胞过表达。Transwell实验和流式细胞术评估了SNX10对卵巢癌细胞转移和顺铂诱导凋亡的影响。进行RNA测序、蛋白质免疫印迹、溶酶体pH检测、脂滴染色和RT-qPCR,以探索SNX10在TAM极化和免疫调节中的分子机制。:SNX10在TAM中特异性表达,促进其极化为M2表型。这增强了卵巢癌细胞系A2780和A2780/CP70的迁移和侵袭,同时减少了顺铂诱导的凋亡。SNX10降低了TAM中的脂滴含量,下调了p-mTOR1,并损害了溶酶体功能。此外,SNX10在铂敏感和铂耐药卵巢癌细胞中差异调节mRNA表达。:SNX10调节TAM中的mTOR1/溶酶体途径,影响脂质代谢并间接调节卵巢癌细胞转移。它还改变mRNA表达,表明在塑造肿瘤免疫微环境中发挥作用。