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
Molecular Cancer
Published in: Molecular Cancer 1/2014

Open Access 01-12-2014 | Research

HMGN2, a new anti-tumor effector molecule of CD8+ T cells

Authors: Lin Su, Ankang Hu, Yang Luo, Wenjie Zhou, Ping Zhang, Yun Feng

Published in: Molecular Cancer | Issue 1/2014

Login to get access

Abstract

Background

Cytolytic T lymphocytes (CTL) and natural killer (NK) cells have been implicated as important cells in antitumor responses. Our previous research has shown that high mobility group nucleosomal-binding domain 2 (HMGN2) could be released by IL-2 and PHA stimulated peripheral blood mononuclear cells (PBMCs) and also induced tumor cells apoptosis at low doses. In this study, we isolated and cultured PBMCs and CD8+ T cells to analyze the expression and antitumor effects of HMGN2.

Methods

PBMCs from healthy donors were isolated using Human Lymphocyte Separation tube. CD8+ T cells were separated from the PBMCs using MoFlo XDP high-speed flow cytometry sorter. Activation of PBMCs and CD8+ T cells were achieved by stimulating with Phytohemagglutinin (PHA) or tumor antigen. In addition, the methods of ELISA, intracellular staining, and fluorescence-labeling assays were used.

Results

PHA induced PBMCs to release high levels of HMGN2, and CD8+ T cells was the major cell population in PBMCs that release HMGN2 after PHA activation. Tumor antigen-activated CD8+ T cells also released high levels of HMGN2. Supernatants of tumor antigen-activated CD8+ T cells were able to kill tumor cells in a dose-dependent manner. This antitumor effect could be significantly blocked by using an anti-HMGN2 antibody. Fluorescence-labeling assays showed that the supernatant proteins of activated CD8+ T cells could be transported into tumor cells, and the transport visibly decreased after HMGN2 was depleted by anti-HMGN2 antibody.

Conclusions

These results suggest that HMGN2 is an anti-tumor effector molecule of CD8+ T cells.
Appendix
Available only for authorised users
Literature
1.
Edwards KM, Davis JE, Browne KA, Sutton VR, Trapani JA: Anti-viral strategies of cytotoxic T lymphocytes are manifested through a variety of granule-bound pathways of apoptosis induction. Immunol Cell Biol. 1999, 77: 76-89. 10.1046/j.1440-1711.1999.00799.xCrossRefPubMed
2.
Anderson DH, Sawaya MR, Cascio D, Ernst W, Modlin R, Krensky A, Eisenberg D: Granulysin crystal structure and a structure-derived lytic mechanism. J Mol Biol. 2003, 325: 355-365. 10.1016/S0022-2836(02)01234-2CrossRefPubMed
3.
Kumar J, Okada S, Clayberger C, Krensky AM: Granulysin: a novel antimicrobial. Expert Opin Investig Drugs. 2001, 10: 321-329. 10.1517/13543784.10.2.321CrossRefPubMed
4.
5.
Beyaert B, Beaugerie L, Assche GV, Brochez L, Renauld JC, Viguier M, Cocquyt V, Jerusalem G, Machiels JP, Prenen H, Masson P, Louis E, Keyser FD: Cancer risk in immune-mediated inflammatory diseases (IMID). Mol Cancer. 2013, 12: 98-109. 10.1186/1476-4598-12-98PubMedCentralCrossRefPubMed
6.
Feng Y, Huang N, Wu Q, Wang BY: HMGN2: a novel antimicrobial effector molecule of human mononuclear leukocytes?. J Leukoc Biol. 2005, 78: 1136-1141. 10.1189/jlb.0505280CrossRefPubMed
7.
Bustin M: Regulation of DNA-dependent activities by the functional motifs of the high- mobility- group chromosomal proteins. Mol Cell Biol. 1999, 19: 5237-5246.PubMedCentralCrossRefPubMed
8.
Yang H, Antoine DJ, Andersson U, Tracey KJ: The many faces of HMGB1: molecular structure-functional activity in inflammation, apoptosis, and chemotaxis. J Leukoc Biol. 2013, 93 (6): 865-873. 10.1189/jlb.1212662PubMedCentralCrossRefPubMed
9.
Harris HE, Andersson U, Pisetsky DS: HMGB1: a multifunctional alarmin driving autoimmune and inflammatory disease. Nat Rev Rheumatol. 2012, 8 (4): 195-202. 10.1038/nrrheum.2011.222CrossRefPubMed
10.
Yanai H, Ban T, Wang ZC, Choi MK, Kawamura T, Negishi H, Nakasato M, Lu Y, Hangai S, Koshiba R, Savitsky D, Ronfani L, Akira S, Bianchi ME, Honda K, Tamura T, Kodama T, Taniguchi T: HMGB proteins function as universal sentinels for nucleic-acid-mediated innate immune responses. Nature. 2009, 462: 99-103. 10.1038/nature08512CrossRefPubMed
11.
12.
Birger Y, Ito Y, West KL, Landsman D, Bustin M: HMGN4, a newly discovered nucleosome- binding protein encoded by an intronless gene. DNA Cell Biol. 2001, 20: 257-264.CrossRefPubMed
13.
Bustin M, Reeves R: High-mobility-group chromosomal proteins: architectural components that facilitate chromatin function. Prog Nucleic Acid Res Mol Biol. 1996, 54: 35-100.CrossRefPubMed
14.
West KL, Ito Y, Birger Y, Postnikov Y, Shirakawa H, Bustin M: HMGN3a and HMGN3b, two protein isoforms with a tissue-specific expression pattern, expand the cellular repertoire of nucleosome-binding proteins. J Biol Chem. 2001, 276: 25959-25969. 10.1074/jbc.M101692200CrossRefPubMed
15.
Shirakawa H, Landsman D, Postnikov YV, Bustin M: NBP-45, a novel nucleosomal binding protein with a tissue-specific and developmentally regulated expression. J Biol Chem. 2000, 275: 6368-6374. 10.1074/jbc.275.9.6368CrossRefPubMed
16.
Birger Y, Catez F, Furusawa T, Lim JH, Prymakowska-Bosak M, West KL, Postnikov YV, Haines DC, Bustin M: Increased tumorigenicity and sensitivity to ionizing radiation upon loss of chromosomal protein HMGN1. Cancer Res. 2005, 65: 6711-6718. 10.1158/0008-5472.CAN-05-0310PubMedCentralCrossRefPubMed
17.
Rochman M, Malicet C, Bustin M: HMGN5/NSBP1: A new member of the HMGN protein family that affects chromatin structure and function. Biochim Biophys Acta. 2010, 1799: 86-92. 10.1016/j.bbagrm.2009.09.012PubMedCentralCrossRefPubMed
18.
Li DQ, Hou YF, Wu J, Chen Y, Lu JS, Di GH, Ou ZL, Shen ZZ, Ding J, Shao ZM: Gene expression profile analysis of an isogenic tumourmetastasis model reveals a functional role for oncogene AF1Q in breast cancer metastasis. Eur J Cancer. 2006, 42: 3274-3286. 10.1016/j.ejca.2006.07.008CrossRefPubMed
19.
Tang WY, Newbold R, Mardilovich K, Jefferson W, Cheng RY, Medvedovic M, Ho SM: Persistent hypomethylation in the promoter of nucleosomal binding protein 1 (Nsbp1) correlates with overexpression of Nsbp1 in mouse uteri neonatally exposed to diethylstilbestrol or genistein. Endocrinology. 2008, 149: 5922-5931. 10.1210/en.2008-0682PubMedCentralCrossRefPubMed
20.
Popescu N, Landsman D, Bustin M: Mapping the human gene coding for chromosomal protein HMG-17. Hum Genet. 1990, 85: 376-378.CrossRefPubMed
21.
Okamura S, Ng CC, Koyama K, Takei Y, Arakawa H, Monden M, Nakamura Y: Identification of seven genes regulated by wild-type p53 in a colon cancer cell line carrying a well-controlled wild-type p53 expression system. Oncol Res. 1999, 11: 281-285.PubMed
22.
Bustin M, Reisch J, Einck L, Klippel JH: Autoantibodies to nucleosomal proteins: antibodies to HMG-17 in autoimmune diseases. Science. 1982, 215: 1245-1247. 10.1126/science.6460317CrossRefPubMed
23.
Porkka K, Laakkonen P, Hoffman JA, Bernasconi M, Ruoslahti E: A fragment of the HMGN2 protein homes to the nuclei of tumor cells and tumor endothelial cells in vivo. Proc Natl Acad Sci. 2002, 99: 7444-7449. 10.1073/pnas.062189599PubMedCentralCrossRefPubMed
24.
Hu AK, Dong XQ, Liu XQ, Zhang P, Zhang YH, Su N, Chen QM, Feng Y: The nucleosome binding protein HMGN2 exhibits antitumor activity in oral squamous cell carcinoma. Oncol Lett. 2014, 7: 115-120.PubMedCentralPubMed
25.
Wei DF, Zhang P, Zhou M, Feng Y, Chen QM: HMGN2 protein inhibits the growth of infected T24 cells in vitro. J Cancer Res Ther. 2014, 2 (10): 299-304.
Metadata
Title
HMGN2, a new anti-tumor effector molecule of CD8+ T cells
Authors
Lin Su
Ankang Hu
Yang Luo
Wenjie Zhou
Ping Zhang
Yun Feng
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2014
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-13-178

Other articles of this Issue 1/2014

Molecular Cancer 1/2014 Go to the issue

Research

Tumor suppressor miR-24 restrains gastric cancer progression by downregulating RegIV

Research

Lnc RNA HOTAIR functions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer

Research

microRNA-139-5p exerts tumor suppressor function by targeting NOTCH1 in colorectal cancer

Research

Loss of miR-638 in vitro promotes cell invasion and a mesenchymal-like transition by influencing SOX2 expression in colorectal carcinoma cells

Research

Histone deacetylase inhibition synergistically enhances pemetrexed cytotoxicity through induction of apoptosis and autophagy in non-small cell lung cancer

Short communication

Direct but not indirect co-culture with osteogenically differentiated human bone marrow stromal cells increases RANKL/OPG ratio in human breast cancer cells generating bone metastases
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