한빛사논문
- 조회658
Yeon-Sook Choia,1, Myung Ji Kima,1, Eun A. Choia, Sinae Kima, Eun ji Leea, Min Ji Parka, Mi-Ju Kimb, Yeon Wook Kimb, Hee-Sung Ahnc, Jae Yun Junga, Gayoung Janga, Yongsub Kima, Hyori Kimc, Kyunggon Kimc, Jin Young Kimd, Seung-Mo Honge, Song Cheol Kimf,2, and Suhwan Changa,2
aDepartment of Biomedical Sciences, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, South Korea;
bAsan Institute for Life Sciences, Asan Medical Center, Seoul, 05505, South Korea;
cDepartment of Convergence Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, South Korea;
dResearch Center for Bioconvergence Analysis, Korea Basic Science Institute, Ochang, 28119, South Korea;
eDepartment of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, South Korea; and
fDivision of Hepato-Biliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, South Korea
1Y.-S.C. and M.J.K. contributed equally to this work.
2To whom correspondence may be addressed.
Abstract
The major challenges in pancreatic ductal adenocarcinoma (PDAC) management are local or distant metastasis and limited targeted therapeutics to prevent it. To identify a druggable target in tumor secretome and to explore its therapeutic intervention, we performed a liquid chromatography–tandem mass spectrometry (LC-MS/MS)–based proteomic analysis of tumors obtained from a patient-derived xenograft model of PDAC. Galectin-3 binding protein (Gal-3BP) is identified as a highly secreted protein, and its overexpression is further validated in multiple PDAC tumors and primary cells. Knockdown and exogenous treatment of Gal-3BP showed that it is required for PDAC cell proliferation, migration, and invasion. Mechanistically, we revealed that Gal-3BP enhances galectin-3–mediated epidermal growth factor receptor signaling, leading to increased cMyc and epithelial-mesenchymal transition. To explore the clinical impact of these findings, two antibody clones were developed, and they profoundly abrogated the metastasis of PDAC cells in vivo. Altogether, our data demonstrate that Gal-3BP is an important therapeutic target in PDAC, and we propose its blockade by antibody as a therapeutic option for suppressing PDAC metastasis.
논문정보
- Research article
- 2022년 07월 (BRIC 등록일 2022-09-01)
- 국내 연구진
- 의약학 > 종양의학
댓글 작성 로그인
팝업 닫기관련 링크
연구자 키워드
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
