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

2021 ◽  
Author(s):  
Lukas Clemens Böckelmann ◽  
Theresa Felix ◽  
Simona Calabrò ◽  
Udo Schumacher

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.

2020 ◽  
Author(s):  
Ewen Calder ◽  
Anna Skwarska ◽  
Deborah Sneddon ◽  
Lisa Folkes ◽  
Ishna N. Mistry ◽  
...  

The design and synthesis of four hypoxia-activated prodrugs of the KDAC inhibitor panobinostat is described. Initial validation of these compounds using isolated enzymes, and in two human cancer cell lines, reveals that the nitroimidazole-based prodrug (NI-Pano, CH-03) undergoes efficient bioreduction and fragmentation to release the parent drug, panobinostat. NI-Pano was identified as the optimum compound for use in further studies in cells, spheroid tumor models, and <i>in vivo</i>.


Oncotarget ◽  
2016 ◽  
Vol 7 (27) ◽  
pp. 41363-41379 ◽  
Author(s):  
Kowthar Y. Salim ◽  
Saman Maleki Vareki ◽  
Wayne R. Danter ◽  
Serban San-Marina ◽  
James Koropatnick

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