View : 199 Download: 36

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 HyunKim, Taek-KeunKim, Ji WoongCho, Yea BinNa, Hee JunYoo, Byong ChulShim, HyunboSong, Dong-KeunHeo, KyunLee, Sukmook
Ewha Authors
심현보
SCOPUS Author ID
심현보scopus
Issue Date
2019
Journal Title
BIOMOLECULES
ISSN
2218-273XJCR Link
Citation
BIOMOLECULES vol. 9, no. 11
Keywords
cetuximab resistanceGRP94human antibodycolorectal cancer
Publisher
MDPI
Indexed
SCIE; SCOPUS WOS 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:
Antibody-Based Targeting.pdf(2.63 MB) Download
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE