anti-EGFR capture mitigates EMT- and chemoresistance-associated heterogeneity in a resistance-profiling CTC platform

Analytical Biochemistry
Fredrik I ThegeBrian J Kirby

Abstract

Capture and analysis of circulating tumor cells (CTCs) holds promise for diagnosing and guiding treatment of pancreatic cancer. To accurately monitor disease progression, capture platforms must be robust to processes that increase the phenotypic heterogeneity of CTCs. Most CTC-analysis technologies rely on the recognition of epithelial-specific markers for capture and identification, in particular the epithelial cell-adhesion molecule (EpCAM) and cytokeratin. As the epithelial-to-mesenchymal transition (EMT) and the acquisition of chemoresistance are both associated with loss of epithelial markers and characteristics, the effect of these processes on the expression of commonly used CTC markers, specifically EpCAM, EGFR and cytokeratin, requires further exploration. To determine this effect, we developed an in vitro model of EMT and acquired gemcitabine resistance in human pancreatic cancer cell lines. Using this model, we show that EMT-induction and acquired chemoresistance decrease EpCAM expression and microfluidic anti-EpCAM capture performance. Furthermore, we find that EGFR capture is more robust to these processes. By measuring the expression of known mediators of chemoresistance in captured cells using automated imaging a...Continue Reading

Citations

Jul 18, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Lulu HanLingyun Jia
Dec 2, 2020·Cancers·Peng LiuMichiel Stevens
Dec 7, 2019·Analytical Chemistry·Malgorzata A WitekSteven A Soper

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