Reference - Detail
| 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 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 9 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | MIA Paca2(RCB2094) HeLa |