YKL-40/CHI3L1 facilitates migration and invasion in HER2 overexpressing breast epithelial progenitor cells and generates a niche for capillary-like network formation.
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.
['Morera|Erika|E|', 'Steinhäuser|Sarah Sophie|SS|', 'Budkova|Zuzana|Z|', 'Ingthorsson|Saevar|S|', 'Kricker|Jennifer|J|', 'Krueger|Aileen|A|', 'Traustadottir|Gunnhildur Asta|GA|', 'Gudjonsson|Thorarinn|T|']
D018929:Cell Culture Techniques D002465:Cell Movement D049109:Cell Proliferation D000071451:Chitinase-3-Like Protein 1 D004847:Epithelial Cells D058750:Epithelial-Mesenchymal Transition D005260:Female D020869:Gene Expression Profiling D055785:Gene Knockdown Techniques D061307:Human Umbilical Vein Endothelial Cells D006801:Humans D042361:Mammary Glands, Human D009389:Neovascularization, Pathologic D018719:Receptor, ErbB-2 D013234:Stem Cells
YKL-40/CHI3L1 Migration Epithelial to mesenchymal transition (EMT) Angiogenesis Invasive breast cancer