癌细胞在肿瘤发展过程中同时出现的炎症、血管生成、纤维生成和血管静止细胞因子谱,可协调肿瘤血管新生、进展和转移。

IF 5.1 2区 生物学 Q2 CELL BIOLOGY
Cells Pub Date : 2024-10-20 DOI:10.3390/cells13201739
Elizabeth Skapinker, Emilyn B Aucoin, Haley L Kombargi, Abdulrahman M Yaish, Yunfan Li, Leili Baghaie, Myron R Szewczuk
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引用次数: 0

摘要

细胞因子可促进各种癌症进程,如血管生成、上皮细胞向间质转化(EMT)、侵袭和肿瘤进展,并维持癌症干细胞样细胞(CSCs)。在TME中持续促进肿瘤进展的机制仍有待研究。本研究的数据分析了人胰腺癌小鼠模型在肿瘤发生过程中宿主血清中的炎症、血管生成、纤维化和血管抑制细胞因子谱。将胰腺 MiaPaCa-2-eGFP 癌细胞皮下植入 RAG2xCγ 双突变小鼠体内。在植入癌细胞前和研究结束前每周采集血液样本。我们使用 Bio-Plex 微阵列分析和 Bio-Plex 200 系统分析了肿瘤发生过程中不同时间点每只小鼠血液中提取的促炎细胞因子(IL-1β、IL-10、IFN-γ 和 TNF-α)以及血管生成和纤维化细胞因子(IL-15、IL-18、碱性 FGF、LIF、M-CSF、MIG、MIP-2、PDGF-BB 和 VEGF)。在此,我们发现,在癌细胞定植以促进肿瘤发展的过程中,肿瘤小鼠体内的宿主血管生成因子、纤维生成因子和促炎细胞因子谱分析显示,抑制肿瘤发展的宿主血管生成因子和促炎细胞因子显著减少,而促进肿瘤生长的宿主血管生成因子和促炎细胞因子则显著增加。促炎细胞因子 IL-15、IL-18 和 IL-1β 图谱显示,在肿瘤开始生长的第 35 天后,宿主血清中的促炎细胞因子显著增加。相比之下,宿主血清中的血管舒张细胞因子 TNFα、MIG、M-CSF、IL-10 和 IFNγ 在植入癌细胞后第 5 天显著下降。在第 35 天对肿瘤小鼠进行 OP 处理后,血管舒张细胞因子和纤维化细胞因子仍保持较高水平。这些数据表明,癌细胞对肿瘤的发展具有全新的调节作用。研究结果首次确定了胰腺癌细胞是如何利用宿主细胞因子谱来协调肿瘤发展的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Contemporaneous Inflammatory, Angiogenic, Fibrogenic, and Angiostatic Cytokine Profiles of the Time-to-Tumor Development by Cancer Cells to Orchestrate Tumor Neovascularization, Progression, and Metastasis.

Cytokines can promote various cancer processes, such as angiogenesis, epithelial to mesenchymal transition (EMT), invasion, and tumor progression, and maintain cancer stem-cell-like (CSCs) cells. The mechanism(s) that continuously promote(s) tumors to progress in the TME still need(s) to be investigated. The data in the present study analyzed the inflammatory, angiogenic, fibrogenic, and angiostatic cytokine profiles in the host serum during tumor development in a mouse model of human pancreatic cancer. Pancreatic MiaPaCa-2-eGFP cancer cells were subcutaneously implanted in RAG2xCγ double mutant mice. Blood samples were collected before cancer cell implantation and every week until the end point of the study. The extracted serum from the blood of each mouse at different time points during tumor development was analyzed using a Bio-Plex microarray analysis and a Bio-Plex 200 system for proinflammatory (IL-1β, IL-10, IFN-γ, and TNF-α) and angiogenic and fibrogenic (IL-15, IL-18, basic FGF, LIF, M-CSF, MIG, MIP-2, PDGF-BB, and VEGF) cytokines. Here, we find that during cancer cell colonization for tumor development, host angiogenic, fibrogenic, and proinflammatory cytokine profiling in the tumor-bearing mice has been shown to significantly reduce host angiostatic and proinflammatory cytokines that restrain tumor development and increase those for tumor growth. The proinflammatory cytokines IL-15, IL-18, and IL-1β profiles reveal a significant host serum increase after day 35 when the tumor began to progress in growth. In contrast, the angiostatic cytokine profiles of TNFα, MIG, M-CSF, IL-10, and IFNγ in the host serum revealed a dramatic and significant decrease after day 5 post-implantation of cancer cells. OP treatment of tumor-bearing mice on day 35 maintained high levels of angiostatic and fibrogenic cytokines. The data suggest an entirely new regulation by cancer cells for tumor development. The findings identify for the first time how pancreatic cancer cells use host cytokine profiling to orchestrate the initiation of tumor development.

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来源期刊
Cells
Cells Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
9.90
自引率
5.00%
发文量
3472
审稿时长
16 days
期刊介绍: Cells (ISSN 2073-4409) is an international, peer-reviewed open access journal which provides an advanced forum for studies related to cell biology, molecular biology and biophysics. It publishes reviews, research articles, communications and technical notes. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. Full experimental and/or methodical details must be provided.
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