GPI-80 Augments NF-κB Activation in Tumor Cells

Recent studies have discovered a relationship between glycosylphosphatidylinositol (GPI)-anchored protein 80 (GPI-80)/VNN2 (80 kDa GPI-anchored protein) and malignant tumors. GPI-80 is known to regulate neutrophil adhesion; however, the action of GPI-80 on tumors is still obscure. In this study, alt...

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Main Authors: Yuji Takeda, Yuta Kurota, Tomoyuki Kato, Hiromi Ito, Akemi Araki, Hidetoshi Nara, Shinichi Saitoh, Nobuyuki Tanaka, Norihiko Tsuchiya, Hironobu Asao
Format: Article
Language:English
Published: MDPI AG 2021-11-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/21/12027
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author Yuji Takeda
Yuta Kurota
Tomoyuki Kato
Hiromi Ito
Akemi Araki
Hidetoshi Nara
Shinichi Saitoh
Nobuyuki Tanaka
Norihiko Tsuchiya
Hironobu Asao
author_facet Yuji Takeda
Yuta Kurota
Tomoyuki Kato
Hiromi Ito
Akemi Araki
Hidetoshi Nara
Shinichi Saitoh
Nobuyuki Tanaka
Norihiko Tsuchiya
Hironobu Asao
author_sort Yuji Takeda
collection DOAJ
description Recent studies have discovered a relationship between glycosylphosphatidylinositol (GPI)-anchored protein 80 (GPI-80)/VNN2 (80 kDa GPI-anchored protein) and malignant tumors. GPI-80 is known to regulate neutrophil adhesion; however, the action of GPI-80 on tumors is still obscure. In this study, although the expression of GPI-80 mRNA was detectable in several tumor cell lines, the levels of GPI-80 protein were significantly lower than that in neutrophils. To clarify the function of GPI-80 in tumor cells, GPI-80-expressing cells and GPI-80/VNN2 gene-deleted cells were established using PC3 prostate cancer cells. In GPI-80-expressing cells, GPI-80 was mainly detected in vesicles. Furthermore, soluble GPI-80 in the conditioned medium was associated with the exosome marker CD63 and was also detected in the plasma obtained from prostate cancer patients. Unexpectedly, cell adhesion and migration of GPI-80-expressing PC3 cells were not modulated by anti-GPI-80 antibody treatment. However, similar to the GPI-80 family molecule, VNN1, the pantetheinase activity and oxidative state were augmented in GPI-80-expressing cells. GPI-80-expressing cells facilitated non-adhesive proliferation, slow cell proliferation, NF-κB activation and IL-1β production. These phenomena are known to be induced by physiological elevation of the oxidative state. Thus, these observations indicated that GPI-80 affects various tumor responses related to oxidation.
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spelling doaj.art-a5810e6cad8b464db0454c85916ff0622023-11-22T21:01:39ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-11-0122211202710.3390/ijms222112027GPI-80 Augments NF-κB Activation in Tumor CellsYuji Takeda0Yuta Kurota1Tomoyuki Kato2Hiromi Ito3Akemi Araki4Hidetoshi Nara5Shinichi Saitoh6Nobuyuki Tanaka7Norihiko Tsuchiya8Hironobu Asao9Department of Immunology, Faculty of Medicine, Yamagata University, Yamagata 990-9585, JapanDepartment of Urology, Faculty of Medicine, Yamagata University, Yamagata 990-9585, JapanDepartment of Urology, Faculty of Medicine, Yamagata University, Yamagata 990-9585, JapanDepartment of Urology, Faculty of Medicine, Yamagata University, Yamagata 990-9585, JapanDepartment of Immunology, Faculty of Medicine, Yamagata University, Yamagata 990-9585, JapanDepartment of Immunology, Faculty of Medicine, Yamagata University, Yamagata 990-9585, JapanDepartment of Immunology, Faculty of Medicine, Yamagata University, Yamagata 990-9585, JapanDivision of Cancer Biology and Therapeutics, Miyagi Cancer Center Research Institute, Natori 981-1293, JapanDepartment of Urology, Faculty of Medicine, Yamagata University, Yamagata 990-9585, JapanDepartment of Immunology, Faculty of Medicine, Yamagata University, Yamagata 990-9585, JapanRecent studies have discovered a relationship between glycosylphosphatidylinositol (GPI)-anchored protein 80 (GPI-80)/VNN2 (80 kDa GPI-anchored protein) and malignant tumors. GPI-80 is known to regulate neutrophil adhesion; however, the action of GPI-80 on tumors is still obscure. In this study, although the expression of GPI-80 mRNA was detectable in several tumor cell lines, the levels of GPI-80 protein were significantly lower than that in neutrophils. To clarify the function of GPI-80 in tumor cells, GPI-80-expressing cells and GPI-80/VNN2 gene-deleted cells were established using PC3 prostate cancer cells. In GPI-80-expressing cells, GPI-80 was mainly detected in vesicles. Furthermore, soluble GPI-80 in the conditioned medium was associated with the exosome marker CD63 and was also detected in the plasma obtained from prostate cancer patients. Unexpectedly, cell adhesion and migration of GPI-80-expressing PC3 cells were not modulated by anti-GPI-80 antibody treatment. However, similar to the GPI-80 family molecule, VNN1, the pantetheinase activity and oxidative state were augmented in GPI-80-expressing cells. GPI-80-expressing cells facilitated non-adhesive proliferation, slow cell proliferation, NF-κB activation and IL-1β production. These phenomena are known to be induced by physiological elevation of the oxidative state. Thus, these observations indicated that GPI-80 affects various tumor responses related to oxidation.https://www.mdpi.com/1422-0067/22/21/12027IL-1βNF-κBoxidative stresspantetheinaseprostate cancer cells
spellingShingle Yuji Takeda
Yuta Kurota
Tomoyuki Kato
Hiromi Ito
Akemi Araki
Hidetoshi Nara
Shinichi Saitoh
Nobuyuki Tanaka
Norihiko Tsuchiya
Hironobu Asao
GPI-80 Augments NF-κB Activation in Tumor Cells
International Journal of Molecular Sciences
IL-1β
NF-κB
oxidative stress
pantetheinase
prostate cancer cells
title GPI-80 Augments NF-κB Activation in Tumor Cells
title_full GPI-80 Augments NF-κB Activation in Tumor Cells
title_fullStr GPI-80 Augments NF-κB Activation in Tumor Cells
title_full_unstemmed GPI-80 Augments NF-κB Activation in Tumor Cells
title_short GPI-80 Augments NF-κB Activation in Tumor Cells
title_sort gpi 80 augments nf κb activation in tumor cells
topic IL-1β
NF-κB
oxidative stress
pantetheinase
prostate cancer cells
url https://www.mdpi.com/1422-0067/22/21/12027
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