The Use of Human Serum Samples to Study Malignant Transformation: A Pilot Study.

The Use of Human Serum Samples to Study Malignant Transformation: A Pilot Study.
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使用人血清样本研究恶性转化:一项初步研究。

DOI:
10.3390/cells10102670
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发表时间:
2021-10-06
期刊:
影响因子:
6
通讯作者:
Bernard JJ
Bernard JJ
中科院分区:
生物学2区
文献类型:
--
作者:
Holowatyj AN;Gigic B;Warby CA;Ose J;Lin T;Schrotz-King P;Ulrich CM;Bernard JJ

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肥胖和过度肥胖约占所有癌症病例的20%;然而,风险的生物标志物仍有待阐明。尽管成纤维细胞生长因子-2(FGF2)正在成为内脏脂肪组织块的一个有吸引力的候选生物标志物,但循环中的FGF2在恶性转化中的作用仍不清楚。此外,发现生物标记物的功能分析也是有限的。我们试图确定人血清是否可以刺激非致瘤细胞系的3D生长。软琼脂中这种不依赖于锚定的3D生长是细胞系获得性致瘤性的替代标记。我们发现,来自无癌男性和女性的人血清具有在软琼脂中刺激非致瘤上皮细胞JB6P+细胞生长的潜力。在一项对33名男性和女性进行的初步研究中,我们检测了体外恶性转化过程中人类循环中FGF2的水平。血清FGF2水平与上皮细胞集落形成无关(r=0.05,p=0.80),但成纤维细胞生长因子受体-1(FGFR1)选择性抑制剂显著阻断血清刺激的转化,提示FGFR1的FGF2激活可能是必要的,但不足以满足人血清的转化作用。这项初步研究表明FGF2/FGFR1轴在JB6 P+恶性转化中起作用,并描述了一种确定可能促进肿瘤发生的关键血清因子的方法。
Obesity and excess adiposity account for approximately 20% of all cancer cases; however, biomarkers of risk remain to be elucidated. While fibroblast growth factor-2 (FGF2) is emerging as an attractive candidate biomarker for visceral adipose tissue mass, the role of circulating FGF2 in malignant transformation remains unknown. Moreover, functional assays for biomarker discovery are limited. We sought to determine if human serum could stimulate the 3D growth of a non-tumorigenic cell line. This type of anchorage-independent 3D growth in soft agar is a surrogate marker for acquired tumorigenicity of cell lines. We found that human serum from cancer-free men and women has the potential to stimulate growth in soft agar of non-tumorigenic epithelial JB6 P+ cells. We examined circulating levels of FGF2 in humans in malignant transformation in vitro in a pilot study of n = 33 men and women. Serum FGF2 levels were not associated with colony formation in epithelial cells (r = 0.05, p = 0.80); however, a fibroblast growth factor receptor-1 (FGFR1) selective inhibitor significantly blocked serum-stimulated transformation, suggesting that FGF2 activation of FGFR1 may be necessary, but not sufficient for the transforming effects of human serum. This pilot study indicates that the FGF2/FGFR1 axis plays a role in JB6 P+ malignant transformation and describes an assay to determine critical serum factors that have the potential to promote tumorigenesis.
DOI: 10.1158/1055-9965.epi-18-0654
发表时间: 2019-01
期刊: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子: --
作者:
Himbert C;Ose J;Nattenmüller J;Warby CA;Holowatyj AN;Böhm J;Lin T;Haffa M;Gigic B;Hardikar S;Scherer D;Zielske L;Schrotz-King P;Kölsch T;Siegel EM;Shibata D;Ulrich A;Schneider M;Hursting SD;Kauczor HU;Ulrich CM
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期刊: SCIENTIFIC REPORTS
影响因子: 4.6
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发表时间: 2018-01-01
期刊: ADIPOCYTE
影响因子: 3.3
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DOI: 10.1007/s10552-020-01312-1
发表时间: 2020-05-19
影响因子: 2.3
作者:
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通讯作者: Ulrich, Cornelia M.
能量平衡和胃肠癌:风险,干预措施,结果和机制。
DOI: 10.1038/s41575-018-0053-2
发表时间: 2018-11
期刊: Nature reviews. Gastroenterology & hepatology
影响因子: --
作者:
Ulrich CM;Himbert C;Holowatyj AN;Hursting SD
通讯作者: Hursting SD