一种凯莫瑞蛋白肽类似物在两种人结肠癌异种移植小鼠模型中促进肿瘤生长。
A Chemerin Peptide Analog Stimulates Tumor Growth in Two Xenograft Mouse Models of Human Colorectal Carcinoma.
作者信息
Friebus-Kardash Justa, Schulz Petra, Reinicke Sandy, Karthaus Cordula, Schefer Quirino, Bandholtz Sebastian, Grötzinger Carsten
机构信息
Department of Hepatology and Gastroenterology, Charité-University Medicine Berlin, Corporate Member of Free University Berlin and Humboldt University Berlin, 13353 Berlin, Germany.
Department of Nephrology, University Hospital Essen, University Duisburg-Essen, 45127 Essen, Germany.
出版信息
Cancers (Basel). 2021 Dec 28;14(1):125. doi: 10.3390/cancers14010125.
BACKGROUND
Chemerin plasma concentration has been reported to be positively correlated with the risk of colorectal cancer. However, the potential regulation of CRC tumorigenesis and progression has not yet been investigated in an experimental setting. This study addresses this hypothesis by investigating proliferation, colony formation, and migration of CRC cell lines in vitro as well as in animal models.
METHODS
In vitro, microscopic assays to study proliferation, as well as a scratch-wound assay for migration monitoring, were applied using the human CRC cell lines HCT116, HT29, and SW620 under the influence of the chemerin analog CG34. The animal study investigated HCT116-luc and HT29-luc subcutaneous tumor size and bioluminescence during treatment with CG34 versus control, followed by an ex-vivo analysis of vessel density and mitotic activity.
RESULTS
While the proliferation of the three CRC cell lines in monolayers was not clearly stimulated by CG34, the chemerin analog promoted colony formation in three-dimensional aggregates. An effect on cell migration was not observed. In the treatment study, CG34 significantly stimulated both growth and bioluminescence signals of HCT116-luc and HT29-luc xenografts.
CONCLUSIONS
The results of this study represent the first indication of a tumor growth-stimulating effect of chemerin signaling in CRC.
背景
据报道，血浆chemerin浓度与结直肠癌风险呈正相关。然而，尚未在实验环境中研究其对结直肠癌发生和进展的潜在调节作用。本研究通过研究结直肠癌细胞系在体外以及动物模型中的增殖、集落形成和迁移来验证这一假设。
方法
在体外，使用人结直肠癌细胞系HCT116、HT29和SW620，在chemerin类似物CG34的影响下，应用显微镜检测法研究增殖，并采用划痕试验监测迁移。动物研究调查了CG34与对照治疗期间HCT116-luc和HT29-luc皮下肿瘤大小和生物发光情况，随后对血管密度和有丝分裂活性进行离体分析。
结果
虽然CG34未明显刺激三种结直肠癌细胞系在单层中的增殖，但chemerin类似物促进了三维聚集体中的集落形成。未观察到对细胞迁移的影响。在治疗研究中，CG34显著刺激了HCT116-luc和HT29-luc异种移植瘤的生长和生物发光信号。
结论
本研究结果首次表明chemerin信号在结直肠癌中具有促进肿瘤生长的作用。
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