Cellular Oncology ( IF 6.6 ) Pub Date : 2021-08-25 , DOI: 10.1007/s13402-021-00630-z Lukas Clemens Böckelmann 1, 2 , Theresa Felix 1 , Simona Calabrò 1 , Udo Schumacher 1
Background
YKL-40, also known as non-enzymatic chitinase-3 like-protein-1 (CHI3L1), is a glycoprotein expressed and secreted mainly by inflammatory cells and tumor cells. Accordingly, several studies demonstrated elevated YKL-40 serum levels in cancer patients and found YKL-40 to be correlated with a poor prognosis and disease severity in some tumor entities. YKL-40 was suggested to be involved in angiogenesis and extracellular matrix remodeling. As yet, however, its precise biological function remains elusive.
Methods
As YKL-40 protein expression has only been investigated in few malignancies, we employed immunohistochemical detection in a large multi-tumor tissue microarray consisting of 2,310 samples from 72 different tumor entities. In addition, YKL-40 protein expression was determined in primary mouse xenograft tumors derived from human cancer cell lines.
Results
YKL-40 could be detected in almost all cancer entities and was differently expressed depending on tumor stage and subtype (e.g., thyroid cancer, colorectal cancer, gastric cancer and ovarian cancer). While YKL-40 was absent in in vitro grown human cancer cell lines, YKL-40 expression was upregulated in xenograft tumor tissues in vivo.
Conclusions
These data provide new insights into YKL-40 expression at the protein level in various tumor entities and its regulation in tumor models. Our data suggest that upregulation of YKL-40 expression is a common feature in vivo and is finely regulated by tumor cell-microenvironment interactions.
中文翻译:
YKL-40 蛋白在人类肿瘤样本和人类肿瘤细胞系异种移植物中的表达:其在肿瘤模型中的应用意义
背景
YKL-40,也称为非酶几丁质酶3样蛋白1(CHI3L1),是一种主要由炎症细胞和肿瘤细胞表达和分泌的糖蛋白。因此,一些研究表明癌症患者的 YKL-40 血清水平升高,并发现 YKL-40 与某些肿瘤实体的不良预后和疾病严重程度相关。YKL-40 被认为参与血管生成和细胞外基质重塑。然而,到目前为止,它的精确生物学功能仍然难以捉摸。
方法
由于 YKL-40 蛋白表达仅在少数恶性肿瘤中进行了研究,我们在由来自 72 个不同肿瘤实体的 2,310 个样本组成的大型多肿瘤组织微阵列中采用免疫组织化学检测。此外,在源自人类癌细胞系的原代小鼠异种移植肿瘤中测定了 YKL-40 蛋白表达。
结果
YKL-40 可以在几乎所有癌症实体中检测到,并且根据肿瘤分期和亚型(例如,甲状腺癌、结肠直肠癌、胃癌和卵巢癌)的不同而有不同的表达。虽然体外培养的人类癌细胞系中不存在 YKL-40,但体内异种移植肿瘤组织中 YKL-40 的表达上调。
结论
这些数据为各种肿瘤实体中蛋白质水平的 YKL-40 表达及其在肿瘤模型中的调节提供了新的见解。我们的数据表明,YKL-40 表达的上调是体内的一个共同特征,并且受到肿瘤细胞-微环境相互作用的精细调节。