脑皮质细胞条件培养基通过 CXCL10 信号诱导 SK-MEL-28 侵袭

IF 1.9 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Interferon and Cytokine Research Pub Date : 2024-05-01 Epub Date: 2024-03-20 DOI:10.1089/jir.2023.0158
Maria Clara Pinheiro Duarte Sampaio, Renata Virgínia Cavalcanti Santos, Amanda Pinheiro de Barros Albuquerque, Ana Karine de Araújo Soares, Marina Ferraz Cordeiro, Michelle Melgarejo da Rosa, Michelly Cristiny Pereira, Maira Galdino da Rocha Pitta, Moacyr Jesus Barreto de Melo Rêgo
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引用次数: 0

摘要

在各种恶性肿瘤中,黑色素瘤是一种不常见但却很重要的皮肤癌变种,是脑转移的主要原因。尽管人们认识到炎症分子,尤其是趋化因子参与了转移微环境的形成,但脑转移背后错综复杂的细胞信号机制仍然难以捉摸。为了揭示细胞因子在黑色素瘤转移中的作用,我们设计了一种利用混合脑皮质细胞和 SK-MEL-28 黑色素瘤细胞系的方案。与预期相反,我们观察到黑色素瘤细胞暴露于脑条件培养基(CM)后没有明显的形态变化。但是,我们注意到细胞的迁移和增殖都有显著的定量增加。通过分析黑色素瘤对大脑条件培养基的趋化因子分泌情况,我们发现干扰素γ诱导蛋白10(CXCL10)在抑制白细胞介素8(CXCL8)分泌方面起着关键作用。此外,我们还通过透孔试验证明,敲除 CXCL10 会显著降低 SK-MEL-28 细胞系的迁移能力。总之,我们的研究结果表明,在脑转移的背景下,脑CM诱导黑色素瘤细胞迁移,同时调节CXCL10和CXCL8的分泌。这些发现加深了我们对黑色素瘤脑转移潜在机制的理解,为进一步探索和采取有针对性的治疗干预措施铺平了道路。
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Induction of SK-MEL-28 Invasion by Brain Cortical Cell-Conditioned Medium Through CXCL10 Signaling.

Melanoma, an infrequent yet significant variant of skin cancer, emerges as a primary cause of brain metastasis among various malignancies. Despite recognizing the involvement of inflammatory molecules, particularly chemokines, in shaping the metastatic microenvironment, the intricate cellular signaling mechanisms underlying cerebral metastasis remain elusive. In our pursuit to unravel the role of cytokines in melanoma metastasis, we devised a protocol utilizing mixed cerebral cortical cells and SK-MEL-28 melanoma cell lines. Contrary to expectations, we observed no discernible morphological change in melanoma cells exposed to a cerebral conditioned medium (CM). However, a substantial increase in both migration and proliferation was quantitatively noted. Profiling the chemokine secretion by melanoma in response to the cerebral CM unveiled the pivotal role of interferon gamma-induced protein 10 (CXCL10), inhibiting the secretion of interleukin 8 (CXCL8). Furthermore, through a transwell assay, we demonstrated that knockdown CXCL10 led to a significant decrease in the migration of the SK-MEL-28 cell line. In conclusion, our findings suggest that a cerebral CM induces melanoma cell migration, while modulating the secretion of CXCL10 and CXCL8 in the context of brain metastases. These insights advance our understanding of the underlying mechanisms in melanoma cerebral metastasis, paving the way for further exploration and targeted therapeutic interventions.

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来源期刊
CiteScore
3.80
自引率
0.00%
发文量
78
审稿时长
2.2 months
期刊介绍: Journal of Interferon & Cytokine Research (JICR) provides the latest groundbreaking research on all aspects of IFNs and cytokines. The Journal delivers current findings on emerging topics in this niche community, including the role of IFNs in the therapy of diseases such as multiple sclerosis, the understanding of the third class of IFNs, and the identification and function of IFN-inducible genes.
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