RRC ID 67414
Author Nakase I, Kobayashi NB, Takatani-Nakase T, Yoshida T.
Title Active macropinocytosis induction by stimulation of epidermal growth factor receptor and oncogenic Ras expression potentiates cellular uptake efficacy of exosomes.
Journal Sci Rep
Abstract Exosomes are approximately 100-nm vesicles that consist of a lipid bilayer of cellular membranes secreted in large quantities from various types of normal and disease-related cells. Endocytosis has been reported as a major pathway for the cellular uptake of exosomes; however, the detailed mechanisms of their cellular uptake are still unknown. Here, we demonstrate the active induction of macropinocytosis (accompanied by actin reorganisation, ruffling of plasma membrane, and engulfment of large volumes of extracellular fluid) by stimulation of cancer-related receptors and show that the epidermal growth factor (EGF) receptor significantly enhances the cellular uptake of exosomes. We also demonstrate that oncogenic K-Ras-expressing MIA PaCa-2 cells exhibit intensive macropinocytosis that actively transports extracellular exosomes into the cells compared with wild-type K-Ras-expressing BxPC-3 cells. Furthermore, encapsulation of the ribosome-inactivating protein saporin with EGF in exosomes using our simple electroporation method produces superior cytotoxicity via the enhanced cellular uptake of exosomes. Our findings contribute to the biological, pharmaceutical, and medical research fields in terms of understanding the macropinocytosis-mediated cellular uptake of exosomes with applications for exosomal delivery systems.
Volume 5
Pages 10300
Published 2015-6-3
DOI 10.1038/srep10300
PII srep10300
PMID 26036864
PMC PMC4453128
MeSH Biological Transport Epidermal Growth Factor / pharmacology ErbB Receptors / metabolism* Exosomes / metabolism* Gene Expression Regulation, Neoplastic* / drug effects HeLa Cells Humans Pinocytosis* / drug effects Proto-Oncogene Proteins p21(ras) / genetics* Proto-Oncogene Proteins p21(ras) / metabolism* Receptors, CXCR4 / metabolism Ribosome Inactivating Proteins, Type 1 / metabolism Saporins Signal Transduction / drug effects
IF 3.998
Human and Animal Cells MIA Paca2(RCB2094)