Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Cancer Cell International
Published in: Cancer Cell International 1/2009

Open Access 01-12-2009 | Primary research

Localization of CD26/DPPIV in nucleus and its nuclear translocation enhanced by anti-CD26 monoclonal antibody with anti-tumor effect

Authors: Kohji Yamada, Mutsumi Hayashi, Wenlin Du, Kei Ohnuma, Michiie Sakamoto, Chikao Morimoto, Taketo Yamada

Published in: Cancer Cell International | Issue 1/2009

Login to get access

Abstract

Background

CD26 is a type II, cell surface glycoprotein known as dipeptidyl peptidase (DPP) IV. Previous studies have revealed CD26 expression in T cell leukemia/lymphoma and malignant mesothelioma, and an inhibitory effect of anti-CD26 monoclonal antibody (mAb) against the growth of CD26+ cancer cells in vitro and in vivo. The function of CD26 in tumor development is unknown and the machinery with which the CD26 mAb induces its anti-tumor effect remains uncharacterized.

Results

The localization of CD26 in the nucleus of T cell leukemia/lymphoma cells and mesothelioma cells was shown by biochemical and immuno-electron microscopic analysis. The DPPIV enzyme activity was revealed in the nuclear fraction of T cell leukemia/lymphoma cells. These expressions of intra-nuclear CD26 were augmented by treatment with the CD26 mAb, 1F7, with anti-tumor effect against the CD26+ T cell leukemia/lymphoma cells. In contrast, the CD26 mAb, 5F8, without anti-tumor effect, did not augment CD26 expressions in the nucleus. Biotin-labeled, cell surface CD26 translocated into the nucleus constantly, and this translocation was enhanced with 1F7 treatment but not with 5F8.

Conclusion

These results indicate that the intra-nuclear CD26 which moves from plasma membrane may play certain roles in cell growth of human cancer cells.
Appendix
Available only for authorised users
Literature
1.
Havre PA, Abe M, Urasaki Y, Ohnuma K, Morimoto C, Dang NH: The role of CD26/dipeptidyl peptidase IV in cancer. Front Biosci. 2008, 13: 1634-1645. 10.2741/2787.CrossRefPubMed
2.
Kameoka J, Tanaka T, Nojima Y, Schlossman SF, Morimoto C: Direct association of adenosine deaminase with a T cell activation antigen, CD26. Science. 1993, 261 (5120): 466-469. 10.1126/science.8101391.CrossRefPubMed
3.
Dang NH, Torimoto Y, Deusch K, Schlossman SF, Morimoto C: Comitogenic effect of solid-phase immobilized anti-1F7 on human CD4 T cell activation via CD3 and CD2 pathways. J Immunol. 1990, 144 (11): 4092-4100.PubMed
4.
Inamoto T, Yamada T, Ohnuma K, Kina S, Takahashi N, Yamochi T, Inamoto S, Katsuoka Y, Hosono O, Tanaka H, Dang NH, Morimoto C: Humanized anti-CD26 monoclonal antibody as a treatment for malignant mesothelioma tumors. Clin Cancer Res. 2007, 13 (14): 4191-4200. 10.1158/1078-0432.CCR-07-0110.CrossRefPubMed
5.
Inamoto T, Yamochi T, Ohnuma K, Iwata S, Kina S, Inamoto S, Tachibana M, Katsuoka Y, Dang NH, Morimoto C: Anti-CD26 monoclonal antibody-mediated G1-S arrest of human renal clear cell carcinoma Caki-2 is associated with retinoblastoma substrate dephosphorylation, cyclin-dependent kinase 2 reduction, p27(kip1) enhancement, and disruption of binding to the extracellular matrix. Clin Cancer Res. 2006, 12 (11 Pt 1): 3470-3477. 10.1158/1078-0432.CCR-06-0361.CrossRefPubMed
6.
Ho L, Aytac U, Stephens LC, Ohnuma K, Mills GB, McKee KS, Neumann C, LaPushin R, Cabanillas F, Abbruzzese JL, Morimoto C, Dang NH: In vitro and in vivo antitumor effect of the anti-CD26 monoclonal antibody 1F7 on human CD30+ anaplastic large cell T-cell lymphoma Karpas 299. Clin Cancer Res. 2001, 7 (7): 2031-2040.PubMed
7.
Dang NH, Torimoto Y, Sugita K, Daley JF, Schow P, Prado C, Schlossman SF, Morimoto C: Cell surface modulation of CD26 by anti-1F7 monoclonal antibody. Analysis of surface expression and human T cell activation. J Immunol. 1990, 145 (12): 3963-3971.PubMed
8.
Ohnuma K, Ishii T, Iwata S, Hosono O, Kawasaki H, Uchiyama M, Tanaka H, Yamochi T, Dang NH, Morimoto C: G1/S cell cycle arrest provoked in human T cells by antibody to CD26. Immunology. 2002, 107 (3): 325-333. 10.1046/j.1365-2567.2002.01510.x.PubMedCentralCrossRefPubMed
9.
Kotani T, Kawano J, Suganuma T, Hirai K, Umeki K, Aratake Y, Konoe K, Ohtaki S: Immunohistochemical localization of dipeptidyl aminopeptidase IV in thyroid papillary carcinoma. Int J Exp Pathol. 1992, 73 (2): 215-222.PubMedCentralPubMed
10.
Matter K, Stieger B, Klumperman J, Ginsel L, Hauri HP: Endocytosis, recycling, and lysosomal delivery of brush border hydrolases in cultured human intestinal epithelial cells (Caco-2). J Biol Chem. 1990, 265 (6): 3503-3512.PubMed
11.
Tanaka T, Camerini D, Seed B, Torimoto Y, Dang NH, Kameoka J, Dahlberg HN, Schlossman SF, Morimoto C: Cloning and functional expression of the T cell activation antigen CD26. J Immunol. 1992, 149 (2): 481-486.PubMed
12.
Xie Y, Hung MC: Nuclear localization of p185neu tyrosine kinase and its association with transcriptional transactivation. Biochem Biophys Res Commun. 1994, 203 (3): 1589-1598. 10.1006/bbrc.1994.2368.CrossRefPubMed
13.
Lin SY, Makino K, Xia W, Matin A, Wen Y, Kwong KY, Bourguignon L, Hung MC: Nuclear localization of EGF receptor and its potential new role as a transcription factor. Nat Cell Biol. 2001, 3 (9): 802-808. 10.1038/ncb0901-802.CrossRefPubMed
14.
Giri DK, Ali-Seyed M, Li LY, Lee DF, Ling P, Bartholomeusz G, Wang SC, Hung MC: Endosomal transport of ErbB-2: mechanism for nuclear entry of the cell surface receptor. Mol Cell Biol. 2005, 25 (24): 11005-11018. 10.1128/MCB.25.24.11005-11018.2005.PubMedCentralCrossRefPubMed
15.
Maher PA: Nuclear Translocation of fibroblast growth factor (FGF) receptors in response to FGF-2. J Cell Biol. 1996, 134 (2): 529-536. 10.1083/jcb.134.2.529.CrossRefPubMed
16.
Stachowiak MK, Maher PA, Joy A, Mordechai E, Stachowiak EK: Nuclear accumulation of fibroblast growth factor receptors is regulated by multiple signals in adrenal medullary cells. Mol Biol Cell. 1996, 7 (8): 1299-1317.PubMedCentralCrossRefPubMed
17.
Hieda M, Isokane M, Koizumi M, Higashi C, Tachibana T, Shudou M, Taguchi T, Hieda Y, Higashiyama S: Membrane-anchored growth factor, HB-EGF, on the cell surface targeted to the inner nuclear membrane. J Cell Biol. 2008, 180 (4): 763-769. 10.1083/jcb.200710022.PubMedCentralCrossRefPubMed
18.
Lin-Lee YC, Pham LV, Tamayo AT, Fu L, Zhou HJ, Yoshimura LC, Decker GL, Ford RJ: Nuclear localization in the biology of the CD40 receptor in normal and neoplastic human B lymphocytes. J Biol Chem. 2006, 281 (27): 18878-18887. 10.1074/jbc.M513315200.CrossRefPubMed
19.
Wesley UV, McGroarty M, Homoyouni A: Dipeptidyl peptidase inhibits malignant phenotype of prostate cancer cells by blocking basic fibroblast growth factor signaling pathway. Cancer Res. 2005, 65 (4): 1325-1334. 10.1158/0008-5472.CAN-04-1852.CrossRefPubMed
20.
Dignam JD, Lebovitz RM, Roeder RG: Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983, 11 (5): 1475-1489. 10.1093/nar/11.5.1475.PubMedCentralCrossRefPubMed
21.
Kittler JT, Thomas P, Tretter V, Bogdanov YD, Haucke V, Smart TG, Moss SJ: Huntingtin-associated protein 1 regulates inhibitory synaptic transmission by modulating gamma-aminobutyric acid type A receptor membrane trafficking. Proc Natl Acad Sci USA. 2004, 101 (34): 12736-12741. 10.1073/pnas.0401860101.PubMedCentralCrossRefPubMed
22.
Fairfax BP, Pitcher JA, Scott MG, Calver AR, Pangalos MN, Moss SJ, Couve A: Phosphorylation and chronic agonist treatment atypically modulate GABAB receptor cell surface stability. J Biol Chem. 2004, 279 (13): 12565-12573. 10.1074/jbc.M311389200.CrossRefPubMed
23.
Nojima T, Hirose T, Kimura H, Hagiwara M: The interaction between cap-binding complex and RNA export factor is required for intronless mRNA export. J Biol Chem. 2007, 282 (21): 15645-15651. 10.1074/jbc.M700629200.CrossRefPubMed
Metadata
Title
Localization of CD26/DPPIV in nucleus and its nuclear translocation enhanced by anti-CD26 monoclonal antibody with anti-tumor effect
Authors
Kohji Yamada
Mutsumi Hayashi
Wenlin Du
Kei Ohnuma
Michiie Sakamoto
Chikao Morimoto
Taketo Yamada
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2009
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/1475-2867-9-17

Other articles of this Issue 1/2009

Cancer Cell International 1/2009 Go to the issue

Primary research

INTS6/DICE1 inhibits growth of human androgen-independent prostate cancer cells by altering the cell cycle profile and Wnt signaling

Primary research

Increasingly transformed MCF-10A cells have a progressively tumor-like phenotype in three-dimensional basement membrane culture

Primary research

Glucosamine suppresses proliferation of human prostate carcinoma DU145 cells through inhibition of STAT3 signaling

Primary research

Exogenous Cx43 expression decrease cell proliferation rate in rat hepatocarcinoma cells independently of functional gap junction

Primary research

The mRNA expression of SATB1 and SATB2 in human breast cancer

Primary research

Pegylated derivatives of recombinant human arginase (rhArg1) for sustained in vivo activity in cancer therapy: preparation, characterization and analysis of their pharmacodynamics in vivo and in vitro and action upon hepatocellular carcinoma cell (HCC)
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits