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Enhanced internalization of ErbB2 in SK-BR-3 cells with multivalent forms of an artificial ligand
Targeting and down-regulation of ErbB2, a member of EGF receptor family, is regarded as one of the key aspect for cancer treatment because it is often overexpressed in breast and ovarian cancer cells. Although natural ligands for ErbB2 have not been found, unlike other ErbB receptors, EC-1, a 20-ami...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3822962/ https://www.ncbi.nlm.nih.gov/pubmed/21323863 http://dx.doi.org/10.1111/j.1582-4934.2011.01277.x |
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author | Vaidyanath, Arun Hashizume, Toshihiro Nagaoka, Tadahiro Takeyasu, Nao Satoh, Hitomi Chen, Ling Wang, Jiyou Kasai, Tomonari Kudoh, Takayuki Satoh, Ayano Fu, Li Seno, Masaharu |
author_facet | Vaidyanath, Arun Hashizume, Toshihiro Nagaoka, Tadahiro Takeyasu, Nao Satoh, Hitomi Chen, Ling Wang, Jiyou Kasai, Tomonari Kudoh, Takayuki Satoh, Ayano Fu, Li Seno, Masaharu |
author_sort | Vaidyanath, Arun |
collection | PubMed |
description | Targeting and down-regulation of ErbB2, a member of EGF receptor family, is regarded as one of the key aspect for cancer treatment because it is often overexpressed in breast and ovarian cancer cells. Although natural ligands for ErbB2 have not been found, unlike other ErbB receptors, EC-1, a 20-amino acid circular peptide, has been shown to bind to ErbB2 as an artificial ligand. Previously we showed EC-1 peptide did not induce the internalization of ErbB2 in SK-BR-3 cells. In this report, we designed divalent and multivalent forms of EC-1 peptide with the Fc portion of the human IgG and bionanocapsule modified with ZZ-tag on its surface to improve the interaction with ErbB2. These forms showed higher affinity to ErbB2 than that of EC-1 monomer. Furthermore, prominent endosomal accumulation of ErbB2 occurred in SK-BR-3 cells when stimulated with EC-Fc ligand multivalently displayed on the surface of the bionanocapsule, whereas SK-BR-3 cells as themselves displayed stringent mechanism against ErbB2 internalization without stimulation. The multivalent form of EC-1 peptide appeared to internalize ErbB2 more efficiently than divalent form did. This internalization was unaffected by the inhibition of clathrin association, but inhibited when the cholesterol was depleted which explained either caveolar or GPI-AP-early endocytic compartment (GEEC) pathway. Because of the lack of caveolin-1 expression, caveolar machinery may be lost in SK-BR-3 cell line. Therefore, it is suggested that the multivalent form of EC-1 induces the internalization of ErbB2 through the GEEC pathway. |
format | Online Article Text |
id | pubmed-3822962 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-38229622015-04-06 Enhanced internalization of ErbB2 in SK-BR-3 cells with multivalent forms of an artificial ligand Vaidyanath, Arun Hashizume, Toshihiro Nagaoka, Tadahiro Takeyasu, Nao Satoh, Hitomi Chen, Ling Wang, Jiyou Kasai, Tomonari Kudoh, Takayuki Satoh, Ayano Fu, Li Seno, Masaharu J Cell Mol Med Original Articles Targeting and down-regulation of ErbB2, a member of EGF receptor family, is regarded as one of the key aspect for cancer treatment because it is often overexpressed in breast and ovarian cancer cells. Although natural ligands for ErbB2 have not been found, unlike other ErbB receptors, EC-1, a 20-amino acid circular peptide, has been shown to bind to ErbB2 as an artificial ligand. Previously we showed EC-1 peptide did not induce the internalization of ErbB2 in SK-BR-3 cells. In this report, we designed divalent and multivalent forms of EC-1 peptide with the Fc portion of the human IgG and bionanocapsule modified with ZZ-tag on its surface to improve the interaction with ErbB2. These forms showed higher affinity to ErbB2 than that of EC-1 monomer. Furthermore, prominent endosomal accumulation of ErbB2 occurred in SK-BR-3 cells when stimulated with EC-Fc ligand multivalently displayed on the surface of the bionanocapsule, whereas SK-BR-3 cells as themselves displayed stringent mechanism against ErbB2 internalization without stimulation. The multivalent form of EC-1 peptide appeared to internalize ErbB2 more efficiently than divalent form did. This internalization was unaffected by the inhibition of clathrin association, but inhibited when the cholesterol was depleted which explained either caveolar or GPI-AP-early endocytic compartment (GEEC) pathway. Because of the lack of caveolin-1 expression, caveolar machinery may be lost in SK-BR-3 cell line. Therefore, it is suggested that the multivalent form of EC-1 induces the internalization of ErbB2 through the GEEC pathway. Blackwell Publishing Ltd 2011-11 2011-10-24 /pmc/articles/PMC3822962/ /pubmed/21323863 http://dx.doi.org/10.1111/j.1582-4934.2011.01277.x Text en © 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd |
spellingShingle | Original Articles Vaidyanath, Arun Hashizume, Toshihiro Nagaoka, Tadahiro Takeyasu, Nao Satoh, Hitomi Chen, Ling Wang, Jiyou Kasai, Tomonari Kudoh, Takayuki Satoh, Ayano Fu, Li Seno, Masaharu Enhanced internalization of ErbB2 in SK-BR-3 cells with multivalent forms of an artificial ligand |
title | Enhanced internalization of ErbB2 in SK-BR-3 cells with multivalent forms of an artificial ligand |
title_full | Enhanced internalization of ErbB2 in SK-BR-3 cells with multivalent forms of an artificial ligand |
title_fullStr | Enhanced internalization of ErbB2 in SK-BR-3 cells with multivalent forms of an artificial ligand |
title_full_unstemmed | Enhanced internalization of ErbB2 in SK-BR-3 cells with multivalent forms of an artificial ligand |
title_short | Enhanced internalization of ErbB2 in SK-BR-3 cells with multivalent forms of an artificial ligand |
title_sort | enhanced internalization of erbb2 in sk-br-3 cells with multivalent forms of an artificial ligand |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3822962/ https://www.ncbi.nlm.nih.gov/pubmed/21323863 http://dx.doi.org/10.1111/j.1582-4934.2011.01277.x |
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