| Autor: |
Mee Hyun Jeoung, Taek-Keun Kim, Ji Woong Kim, Yea Bin Cho, Hee Jun Na, Byong Chul Yoo, Hyunbo Shim, Dong-Keun Song, Kyun Heo, Sukmook Lee |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
Biomolecules, Vol 9, Iss 11, p 681 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2218-273X |
| DOI: |
10.3390/biom9110681 |
| Popis: |
Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide. Cetuximab, a human/mouse chimeric monoclonal antibody, is effective in a limited number of CRC patients because of cetuximab resistance. This study aimed to identify novel therapeutic targets in cetuximab-resistant CRC in order to improve clinical outcomes. Through phage display technology, we isolated a fully human antibody strongly binding to the cetuximab-resistant HCT116 cell surface and identified the target antigen as glucose-regulated protein 94 (GRP94) using proteomic analysis. Short interfering RNA-mediated GRP94 knockdown showed that GRP94 plays a key role in HCT116 cell growth. In vitro functional studies revealed that the GRP94-blocking antibody we developed strongly inhibits the growth of various cetuximab-resistant CRC cell lines. We also demonstrated that GRP94 immunoglobulin G monotherapy significantly reduces HCT116 cell growth more potently compared to cetuximab, without severe toxicity in vivo. Therefore, cell surface GRP94 might be a potential novel therapeutic target in cetuximab-resistant CRC, and antibody-based targeting of GRP94 might be an effective strategy to suppress GRP94-expressing cetuximab-resistant CRC. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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