학술논문
Glycoprotein nonmetastatic melanoma protein B impacts the malignant potential of bladder cancer cells through its hem-immunoreceptor tyrosine-based activation motif.
Document Type
Academic Journal
Author
Kimura T; Department of Urology, University of Tsukuba, Ibaraki, Japan.; Department of Experimental Pathology, Institute of Medicine, University of Tsukuba, Ibaraki, Japan.; Okita Y; Department of Experimental Pathology, Institute of Medicine, University of Tsukuba, Ibaraki, Japan.; Division of Cell Dynamics, Transborder Medical Research Center, University of Tsukuba, Ibaraki, Japan.; Nagumo Y; Department of Urology, University of Tsukuba, Ibaraki, Japan.; Chin JM; Department of Experimental Pathology, Institute of Medicine, University of Tsukuba, Ibaraki, Japan.; Fikry MA; Department of Experimental Pathology, Institute of Medicine, University of Tsukuba, Ibaraki, Japan.; Shiga M; Department of Urology, University of Tsukuba, Ibaraki, Japan.; Kandori S; Department of Urology, University of Tsukuba, Ibaraki, Japan.; Kawahara T; Department of Urology, University of Tsukuba, Ibaraki, Japan.; Suzuki H; Department of Experimental Pathology, Institute of Medicine, University of Tsukuba, Ibaraki, Japan.; Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, Sendai, Japan.; Nishiyama H; Department of Urology, University of Tsukuba, Ibaraki, Japan.; Kato M; Department of Experimental Pathology, Institute of Medicine, University of Tsukuba, Ibaraki, Japan.; Division of Cell Dynamics, Transborder Medical Research Center, University of Tsukuba, Ibaraki, Japan.
Source
Publisher: Published by Blackwell Scientific Publications for the Japanese Society of Pathology Country of Publication: Australia NLM ID: 9431380 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1440-1827 (Electronic) Linking ISSN: 13205463 NLM ISO Abbreviation: Pathol Int Subsets: MEDLINE
Subject
Language
English
Abstract
Bladder cancer is one of the most common cancers among men worldwide. Although multiple genomic mutations and epigenetic alterations have been identified, an efficacious molecularly targeted therapy has yet to be established. Therefore, a novel approach is anticipated. Glycoprotein nonmetastatic melanoma protein B (GPNMB) is a type I transmembrane glycoprotein that is highly expressed in various cancers. In this study, we evaluated bladder cancer patient samples and found that GPNMB protein abundance is associated with high-grade tumors, and both univariate and multivariate analyses showed that GPNMB is a prognostic factor. Furthermore, the prognosis of patients with high GPNMB levels was significantly poorer in those with nonmuscle invasive bladder cancer (NMIBC) than in those with muscle invasive bladder cancer (MIBC). We then demonstrated that knockdown of GPNMB in MIBC cell lines with high GPNMB inhibits cellular migration and invasion, whereas overexpression of GPNMB further enhances cellular migration and invasion in MIBC cell lines with originally low GPNMB. Therefore, we propose that GPNMB is one of multiple driver molecules in the acquisition of cellular migratory and invasive potential in bladder cancers. Moreover, we revealed that the tyrosine residue in the hemi-immunoreceptor tyrosine-based activation motif (hemITAM) is required for GPNMB-induced cellular motility.
(© 2024 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)
(© 2024 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)