RRC ID 69742
Author Sasabe E, Tomomura A, Liu H, Sento S, Kitamura N, Yamamoto T.
Title Epidermal growth factor/epidermal growth factor receptor signaling blockage inhibits tumor cell-derived exosome uptake by oral squamous cell carcinoma through macropinocytosis.
Journal Cancer Sci
Abstract Various cell types secrete exosomes into their surrounding extracellular space, which consequently affect the function and activity of recipient cells. Numerous studies have showed that tumor cell-derived exosomes play important roles in tumor growth and progression. Although a variety of endocytic pathways are reportedly involved in the cellular uptake of exosomes, detailed mechanisms remain unknown. The present study demonstrated that treatment with recombinant epidermal growth factor (EGF) time- and dose-dependently promoted cellular uptake of oral squamous cell carcinoma (OSCC) cell-derived exosomes into OSCC cells themselves. Conversely, EGF receptor (EGFR) knockdown and treatment with EGFR inhibitors, including erlotinib and cetuximab, abrogated OSCC cell uptake of exosomes. The macropinocytosis inhibitor 5-(N-ethyl-N-isopropyl) amiloride (EIPA) blocked the effects of active EGF/EGFR signaling on uptake of OSCC cell-derived exosomes. These EGFR inhibitors also suppressed OSCC cell-derived exosome-induced proliferation, migration, invasion, stemness, and chemoresistance of OSCC cells. Taken together, the data presented herein suggest that EGFR inhibitors might inhibit the malignant potential of OSCC cells through direct inhibition of not only EGFR downstream signaling pathway but also cellular uptake of OSCC cell-derived exosomes through macropinocytosis.
Volume 113(2)
Pages 609-621
Published 2022-2-1
DOI 10.1111/cas.15225
PMID 34874595
PMC PMC8819298
MeSH Cell Line, Tumor Cell Movement / drug effects Cell Proliferation / drug effects Drug Resistance, Neoplasm / drug effects Epidermal Growth Factor / metabolism* Epidermal Growth Factor / pharmacology ErbB Receptors / antagonists & inhibitors ErbB Receptors / genetics ErbB Receptors / metabolism Exosomes / metabolism* Humans Mouth Neoplasms / metabolism* Mouth Neoplasms / pathology Neoplastic Stem Cells / drug effects Neoplastic Stem Cells / metabolism Pinocytosis* / drug effects Protein Kinase Inhibitors / pharmacology Signal Transduction / drug effects Squamous Cell Carcinoma of Head and Neck / metabolism* Squamous Cell Carcinoma of Head and Neck / pathology
IF 4.966
Human and Animal Cells HSC-2(RCB1945) HSC-3(RCB1975) HSC-4(RCB1902) SAS(RCB1974)