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Early maternal separation enhances melanoma progression in adult female mice by immune mechanisms
Annals of the New York Academy of Sciences ( IF 4.1 ) Pub Date : 2021-06-28 , DOI: 10.1111/nyas.14625
Francisco Stefânio Barreto 1 , Wesley Lyeverton Correia Ribeiro 1 , Bruno Coêlho Cavalcanti 1 , Paulo Goberlânio de Barros Silva 2 , Caren Nádia Soares de Sousa 3 , Germana Silva Vasconcelos 3 , Ana Paula Negreiros Nunes 2 , Manoel Odorico de Moraes Filho 1 , Danielle S Macedo 3, 4
Affiliation  

Maternal separation (MS) is a risk factor for major depressive disorder. Both cancer and depression seem to share a common biological link. Here, we evaluated the progression of melanoma and the underlying mechanisms related to this progression, namely cell proliferation and apoptosis, in adult female mice exposed to MS. Female C57BL/6 mice were exposed to MS for 60 min/day during the first 2 postnatal weeks (here called MS mice) or left undisturbed (here called non-MS mice). Melanoma cells were inoculated subcutaneously into the axillary region of adult animals, and tumor progression was evaluated for 25 days. Adult MS mice presented depressive-like behavior and working memory deficits. MS accelerated murine melanoma growth by mechanisms related to decreased apoptosis and increased cell proliferation rate, such as increased expression of IL-6 and mTOR. MS stimulated eukaryotic elongation factor 2 expression and increased the number of circulating monocytes and DNA damage in peripheral blood leukocytes, an effect associated with oxidative DNA damage. In conclusion, MS accelerated the progression of murine melanoma by mechanisms related to tumor proliferation and apoptosis, revealing a relationship between adverse childhood experiences and cancer progression, particularly melanoma.

中文翻译:

早期母体分离通过免疫机制促进成年雌性小鼠黑色素瘤的进展

母体分离 (MS) 是重度抑郁症的危险因素。癌症和抑郁症似乎有着共同的生物学联系。在这里,我们评估了暴露于 MS 的成年雌性小鼠中黑色素瘤的进展以及与这种进展相关的潜在机制,即细胞增殖和凋亡。雌性 C57BL/6 小鼠在出生后的前 2 周(此处称为 MS 小鼠)或不受干扰(此处称为非 MS 小鼠)暴露于 MS 60 分钟/天。将黑色素瘤细胞皮下接种到成年动物的腋窝区域,并评估肿瘤进展 25 天。成年 MS 小鼠表现出类似抑郁的行为和工作记忆缺陷。MS 通过与细胞凋亡减少和细胞增殖率增加相关的机制加速小鼠黑色素瘤的生长,例如增加 IL-6 和 mTOR 的表达。MS 刺激真核延伸因子 2 表达并增加循环单核细胞的数量和外周血白细胞中的 DNA 损伤,这种作用与氧化性 DNA 损伤相关。总之,MS通过与肿瘤增殖和细胞凋亡相关的机制加速了鼠黑色素瘤的进展,揭示了不良童年经历与癌症进展之间的关系,尤其是黑色素瘤。
更新日期:2021-06-28
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