YKL-40/CHI3L1 facilitates migration and invasion in HER2 overexpressing breast epithelial progenitor cells and generates a niche for capillary-like network formation

• Published in: In Vitro Cellular & Developmental Biology - Animal
• Main Authors: Morera, Erika, Steinhäuser, Sarah Sophie, Budkova, Zuzana, Ingthorsson, Saevar, Kricker, Jennifer, Krueger, Aileen, Traustadottir, Gunnhildur Asta, Gudjonsson, Thorarinn
• Other Authors: Læknadeild (HÍ), Faculty of Medicine (UI), Biomedical Center (UI), Lífvísindasetur (HÍ), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland
• Format: Article in Journal/Newspaper
• Language: English
• Published: Springer Science and Business Media LLC 2019
• Subjects: Angiogenesis; Epithelial to mesenchymal transition (EMT); Invasive breast cancer; Migration; YKL-40/CHI3L1; Brjóstakrabbamein; Krabbameinsrannsóknir; Frumulíffræði; Gen; Iceland
• Online Access: https://hdl.handle.net/20.500.11815/1536; https://doi.org/10.1007/s11626-019-00403-x

Publisher's version (útgefin grein). Epithelial to mesenchymal transition (EMT) is a developmental event that is hijacked in some diseases such as fibrosis and cancer. In cancer, EMT has been linked to increased invasion and metastasis and is generally associated with a poor prognosis. In this study, we have compared phenotypic and functional differences between two isogenic cell lines with an EMT profile: D492M and D492HER2 that are both derived from D492, a breast epithelial cell line with stem cell properties. D492M is non-tumorigenic while D492HER2 is tumorigenic. Thus, the aim of this study was to analyze the expression profile of these cell lines, identify potential oncogenes, and evaluate their effects on cellular phenotype. We performed transcriptome and secretome analyses of D492M and D492HER2 and verified expression of selected genes at the RNA and protein level. One candidate, YKL-40 (also known as CHI3L1), was selected for further studies due to its differential expression between D492M and D492HER2, being considerably higher in D492HER2. YKL-40 has been linked to chronic inflammation diseases and cancer, yet its function is not fully understood. Knock-down experiments of YKL-40 in D492HER2 resulted in reduced migration and invasion as well as reduced ability to induce angiogenesis in an in vitro assay, plus changes in the EMT-phenotype. In summary, our data suggest that YKL-40 may provide D492HER2 with increased aggressiveness, supporting cancer progression and facilitating angiogenesis. This work was supported by Grants from Landspitali University Hospital Science Fund, University of Iceland Research Fund, and Icelandic Science and Technology Policy—Grant of Excellence: 152144051. ‘Göngum saman,’ a supporting group for breast cancer research in Iceland ( www.gongumsaman.is ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Peer Reviewed