Impact of chronic exposure to bevacizumab on EpCAM-based detection of circulating tumor cells

作者: Isabella Massimi , Lavinia V. Lotti , Chiara Nicolazzo , Fabio Maria Pulcinelli , Angela Gradilone

DOI: 10.3978/J.ISSN.1000-9604.2015.04.09

关键词: ImmunofluorescenceColorectal cancerMesenchymal stem cellEpithelial–mesenchymal transitionCancer researchBevacizumabPathologyMedicineEpithelial cell adhesion moleculeCell cultureCirculating tumor cell

摘要: Background: Circulating tumor cells (CTCs) are often undetected through the immunomagnetic epithelial cell adhesion molecule (EpCAM)-based CellSearch ® System in breast and colorectal cancer (CRC) patients treated with bevacizumab (BEV), where low CTC numbers have been reported even evidence of progression disease. To date, reasons for this discrepancy not clarified. This study was carried out to investigate molecular phenotypic changes CRC after chronic exposure BEV vitro . Methods: The human line WiDr exposed a clinically relevant dose 3 months . expression mesenchymal markers EpCAM isoforms determined by western blotting immunofluorescence. evaluate impact variant on enumeration , untreated colon were spiked into 7.5 mL blood from healthy donor enumerated Results: Chronic induced decreased 40 kDa isoform increased 42 isoform, together cytokeratins (CK), while no transition (EMT) observed. recovery rate gradually reduced course treatment BEV, being 84%, 70% 40% at 1, 2 months, respectively. Conclusions: We hypothesize that may prevent capturing CTCs altering isoforms.

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