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An antitumor peptide RS17‐targeted CD47, design, synthesis, and antitumor activity
BACKGROUND: CD47 is a widely expressed transmembrane protein located on the surface of somatic cells. It mediates a variety of cellular processes including apoptosis, proliferation, adhesion, and migration. An important role for CD47 is the transmission of a “Don't eat me” signal by interacting...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957188/ https://www.ncbi.nlm.nih.gov/pubmed/33629544 http://dx.doi.org/10.1002/cam4.3768 |
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author | Wang, Xinmin Wang, Ying Hu, Jialiang Xu, Hanmei |
author_facet | Wang, Xinmin Wang, Ying Hu, Jialiang Xu, Hanmei |
author_sort | Wang, Xinmin |
collection | PubMed |
description | BACKGROUND: CD47 is a widely expressed transmembrane protein located on the surface of somatic cells. It mediates a variety of cellular processes including apoptosis, proliferation, adhesion, and migration. An important role for CD47 is the transmission of a “Don't eat me” signal by interacting with SIRPα on the macrophage surface membrane, thereby preventing the phagocytosis of normal cells. However, cancer cells can take advantage of this autogenous signal to protect themselves from phagocytosis, thus enabling immune escape. Blocking the interaction between CD47 and SIRPα has proven to be effective in removing cancer cells. The treatment of various cancers with CD47 monoclonal antibodies has also been validated. METHODS: We designed and synthesized a peptide (RS17), which can specifically bind to CD47 and block CD47‐SIRPα signaling. The affinity of RS17 for CD47‐expressing tumor cells was determined, while the inhibition of CD47‐SIRPα signaling was evaluated in vitro and in vivo. RESULTS: The results indicated that RS17 significantly promotes the phagocytosis of tumor cells by macrophages and had a similar therapeutic effect compared with a positive control (CD47 monoclonal antibodies). In addition, a cancer xenograft mouse model was established using CD47‐expressing HepG2 cells to evaluate the effect of RS17 on tumor growth in vivo. Using ex vivo and in vivo mouse models, RS17 demonstrated a high inhibitory effect on tumor growth. CONCLUSIONS: Based on our results, RS17 may represent a novel therapeutic peptide for cancer therapy. |
format | Online Article Text |
id | pubmed-7957188 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-79571882021-03-19 An antitumor peptide RS17‐targeted CD47, design, synthesis, and antitumor activity Wang, Xinmin Wang, Ying Hu, Jialiang Xu, Hanmei Cancer Med Cancer Biology BACKGROUND: CD47 is a widely expressed transmembrane protein located on the surface of somatic cells. It mediates a variety of cellular processes including apoptosis, proliferation, adhesion, and migration. An important role for CD47 is the transmission of a “Don't eat me” signal by interacting with SIRPα on the macrophage surface membrane, thereby preventing the phagocytosis of normal cells. However, cancer cells can take advantage of this autogenous signal to protect themselves from phagocytosis, thus enabling immune escape. Blocking the interaction between CD47 and SIRPα has proven to be effective in removing cancer cells. The treatment of various cancers with CD47 monoclonal antibodies has also been validated. METHODS: We designed and synthesized a peptide (RS17), which can specifically bind to CD47 and block CD47‐SIRPα signaling. The affinity of RS17 for CD47‐expressing tumor cells was determined, while the inhibition of CD47‐SIRPα signaling was evaluated in vitro and in vivo. RESULTS: The results indicated that RS17 significantly promotes the phagocytosis of tumor cells by macrophages and had a similar therapeutic effect compared with a positive control (CD47 monoclonal antibodies). In addition, a cancer xenograft mouse model was established using CD47‐expressing HepG2 cells to evaluate the effect of RS17 on tumor growth in vivo. Using ex vivo and in vivo mouse models, RS17 demonstrated a high inhibitory effect on tumor growth. CONCLUSIONS: Based on our results, RS17 may represent a novel therapeutic peptide for cancer therapy. John Wiley and Sons Inc. 2021-02-24 /pmc/articles/PMC7957188/ /pubmed/33629544 http://dx.doi.org/10.1002/cam4.3768 Text en © 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Cancer Biology Wang, Xinmin Wang, Ying Hu, Jialiang Xu, Hanmei An antitumor peptide RS17‐targeted CD47, design, synthesis, and antitumor activity |
title | An antitumor peptide RS17‐targeted CD47, design, synthesis, and antitumor activity |
title_full | An antitumor peptide RS17‐targeted CD47, design, synthesis, and antitumor activity |
title_fullStr | An antitumor peptide RS17‐targeted CD47, design, synthesis, and antitumor activity |
title_full_unstemmed | An antitumor peptide RS17‐targeted CD47, design, synthesis, and antitumor activity |
title_short | An antitumor peptide RS17‐targeted CD47, design, synthesis, and antitumor activity |
title_sort | antitumor peptide rs17‐targeted cd47, design, synthesis, and antitumor activity |
topic | Cancer Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957188/ https://www.ncbi.nlm.nih.gov/pubmed/33629544 http://dx.doi.org/10.1002/cam4.3768 |
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