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Antibody-Based Targeting of Cell Surface GRP94 Specifically Inhibits Cetuximab-Resistant Colorectal Cancer Growth
- Title
- Antibody-Based Targeting of Cell Surface GRP94 Specifically Inhibits Cetuximab-Resistant Colorectal Cancer Growth
- Authors
- Jeoung, Mee Hyun; Kim, Taek-Keun; Kim, Ji Woong; Cho, Yea Bin; Na, Hee Jun; Yoo, Byong Chul; Shim, Hyunbo; Song, Dong-Keun; Heo, Kyun; Lee, Sukmook
- Ewha Authors
- 심현보
- SCOPUS Author ID
- 심현보
- Issue Date
- 2019
- Journal Title
- BIOMOLECULES
- ISSN
- 2218-273X
- Citation
- BIOMOLECULES vol. 9, no. 11
- Keywords
- cetuximab resistance; GRP94; human antibody; colorectal cancer
- Publisher
- MDPI
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- 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.
- DOI
- 10.3390/biom9110681
- Appears in Collections:
- 일반대학원 > 바이오융합과학과 > Journal papers
- Files in This Item:
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