Sialidase Attenuates Epidermal Growth Factor Response and Abolishes Antiproliferative Effects of Erlotinib in A549Alveolar Epithelial Cells.
Erlotinib is a widely used, reversible tyrosine kinase inhibitor (TKI), targeting pro-proliferative signaling of epidermal growth factor receptor (EGFR). The drug is approved for the first-line treatment of patients with metastatic non-small cell lung cancer with EGFR mutations. Extracellular glycans can affect EGFR expression, dimerization, phosphorylation, and EGF binding. In this study we investigated the effects of EGF and erlotinib on the cell cycle of naive and sialidase (alpha-neuraminidase)-pretreated human A549 alveolar epithelial cells. A549 cells were labeled with propidium iodide, and fractions of cells in different phases of cycle were quantified by flow cytometry. We found that neither did desialilation nor EGF, as well as erlotinib treatment, increase the number of damaged cells (subG0/G1 cell fraction), while erlotinib did significantly increase the number of G0/G1 cells and decrease S + G2/M cell fractions. In naive cells, EGF increased proliferating cell numbers by more than 40%, and this effect was blocked by erlotinib. In desialylated cells, however, proliferation was significantly decreased by about 29%, and EGF and erlotinib did not exert significant effects. We conclude that changes in alveolar epithelial cell membrane glycosylation may affect function of growth-promoting receptors and erlotinib effectiveness.
['Rybak|A|A|', 'Zarzecki|M|M|', 'Golabiewska|E|E|', 'Niechoda|A|A|', 'Holownia|A|A|']
D002289:Carcinoma, Non-Small-Cell Lung D045744:Cell Line, Tumor D004815:Epidermal Growth Factor D004847:Epithelial Cells D000069347:Erlotinib Hydrochloride D006801:Humans D008175:Lung Neoplasms D009439:Neuraminidase D047428:Protein Kinase Inhibitors D011799:Quinazolines
Sialidase Epidermal growth factor Erlotinib Cell cycle Alveolar epithelial cells A549 cells