YKL-40 protein expression in human tumor samples and human tumor cell line xenografts: implications for its use in tumor models

Cell Oncol (Dordr). 2021 Oct;44(5):1183-1195. doi: 10.1007/s13402-021-00630-z. Epub 2021 Aug 25.

Abstract

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.

Keywords: CHI3L1; Cancer; Immunohistochemistry; Tissue array; Tumorigenesis; Xenograft; YKL-40.

MeSH terms

  • Animals
  • Caco-2 Cells
  • Cell Line, Tumor
  • Chitinase-3-Like Protein 1 / biosynthesis
  • Chitinase-3-Like Protein 1 / blood
  • Chitinase-3-Like Protein 1 / genetics*
  • Gene Expression Regulation, Neoplastic*
  • HCT116 Cells
  • HT29 Cells
  • Humans
  • Immunohistochemistry
  • MCF-7 Cells
  • Mice
  • Mice, SCID
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Prognosis
  • Transcriptome / genetics*
  • Transplantation, Heterologous
  • Tumor Microenvironment / genetics*

Substances

  • CHI3L1 protein, human
  • Chitinase-3-Like Protein 1