Role of Extracellular High-Mobility Group Box-1 As a Therapeutic Target of Gastric Cancer

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Mar 25

PMID 35328684

Authors

Wataru Takaki

Hirotaka Konishi

Daiki Matsubara

Katsutoshi Shoda

Tomohiro Arita

Satoshi Kataoka

Jun Shibamoto

Hirotaka Furuke

Kazuya Takabatake

Hiroki Shimizu

Shuhei Komatsu

Atsushi Shiozaki

Takeshi Kubota

Kazuma Okamoto

Eigo Otsuji

Affiliations

Soon will be listed here.

Abstract

Background: High-mobility group box-1 (HMGB1) is involved in the tumorigenesis and metastasis of various cancers. The present study investigated the roles of extracellular HMGB1 in the progression of gastric cancer (GC) and the therapeutic effects of recombinant human soluble thrombomodulin (rTM) targeting HMGB1. Methods: The effects of extracellular HMGB1 and rTM on GC cells were assessed using proliferation and Transwell assays. Their effects on local tumor growth and metastasis were evaluated using subcutaneous tumor and liver metastasis mouse models, respectively. Plasma HMGB1 concentrations in GC patients were measured using ELISA. The relationships between plasma HMGB1 concentrations and the prognosis and clinicopathological factors of patients were also investigated. Results: GC proliferation, migration, and invasion abilities were promoted by increases in extracellular HMGB1 concentrations and alleviated by rTM. In the subcutaneous tumor model, local tumor growth was promoted by the addition of rhHMGB1 and alleviated by rTM. Similar changes occurred in the liver metastasis model. Recurrence-free survival (p < 0.01) and overall survival (p = 0.01) were significantly worse in patients with high plasma HMGB1 concentrations. Conclusion: Plasma HMGB1 concentrations are a prognostic marker in GC patients. Extracellular HMGB1 promotes cancer progression and has potential as a novel treatment target in GC cells for rTM.

Citing Articles

The mechanism of high mobility group box-1 protein and its bidirectional regulation in tumors.

Tian Z, Zhu L, Xie Y, Hu H, Ren Q, Liu J Biomol Biomed. 2023; 24(3):477-485.

PMID: 37897664 PMC: 11088895. DOI: 10.17305/bb.2023.9760.

Function of as a competing endogenous RNA to promote progression in gastric cancer by regulating the axis.

Qin J, Zhen S, Wang J, Lv W, Zhao Y, Duan Y J Gastrointest Oncol. 2023; 14(3):1259-1278.

PMID: 37435216 PMC: 10331750. DOI: 10.21037/jgo-23-240.

Obesity paradox as a new insight from postoperative complications in gastric cancer.

Kamiya H, Komatsu S, Nishibeppu K, Ohashi T, Konishi H, Shiozaki A Sci Rep. 2023; 13(1):10116.

PMID: 37344511 PMC: 10284837. DOI: 10.1038/s41598-023-36968-7.

Gastric alarmin release: A warning signal in the development of gastric mucosal diseases.

Wu E, Zhu J, Ma Z, Tuo B, Terai S, Mizuno K Front Immunol. 2022; 13:1008047.

PMID: 36275647 PMC: 9583272. DOI: 10.3389/fimmu.2022.1008047.

References

Yamakawa K, Aihara M, Ogura H, Yuhara H, Hamasaki T, Shimazu T . Recombinant human soluble thrombomodulin in severe sepsis: a systematic review and meta-analysis. J Thromb Haemost. 2015; 13(4):508-19. DOI: 10.1111/jth.12841. View

Sano T, Coit D, Kim H, Roviello F, Kassab P, Wittekind C . Proposal of a new stage grouping of gastric cancer for TNM classification: International Gastric Cancer Association staging project. Gastric Cancer. 2016; 20(2):217-225. PMC: 4992472. DOI: 10.1007/s10120-016-0601-9. View

Oda H, Nagamatsu T, Schust D, Cabral H, Miyazaki T, Iriyama T . Recombinant Thrombomodulin Attenuates Preeclamptic Symptoms by Inhibiting High-Mobility Group Box 1 in Mice. Endocrinology. 2021; 162(4). DOI: 10.1210/endocr/bqaa248. View

Oda H, Nagamatsu T, Cabral H, Miyazaki T, Iriyama T, Kawana K . Thrombomodulin promotes placental function by up-regulating placental growth factor via inhibition of high-mobility-group box 1 and hypoxia-inducible factor 1α. Placenta. 2021; 111:1-9. DOI: 10.1016/j.placenta.2021.06.002. View

He S, Cheng J, Sun L, Wang Y, Wang C, Liu X . HMGB1 released by irradiated tumor cells promotes living tumor cell proliferation via paracrine effect. Cell Death Dis. 2018; 9(6):648. PMC: 5974346. DOI: 10.1038/s41419-018-0626-6. View

Kuo A, Scheeren F . Cell-intrinsic TLR2/MyD88 pathway in breast and colon cancer. Cell Cycle. 2014; 13(24):3785-6. PMC: 4612108. DOI: 10.4161/15384101.2014.989947. View

Zhang Q, Wu L, Zhang T, Han Y, Lin X . Autophagy-mediated HMGB1 release promotes gastric cancer cell survival via RAGE activation of extracellular signal-regulated kinases 1/2. Oncol Rep. 2015; 33(4):1630-8. PMC: 4358082. DOI: 10.3892/or.2015.3782. View

Wang Q, Liu Q, Wang T, Yang H, Han Z, Zhang P . Endothelial cell protein C receptor promotes MGC803 gastric cancer cells proliferation and migration by activating ERK1/2. Med Oncol. 2015; 32(5):162. DOI: 10.1007/s12032-015-0614-y. View

Kawasoe J, Uchida Y, Miyauchi T, Kadono K, Hirao H, Saga K . The lectin-like domain of thrombomodulin is a drug candidate for both prophylaxis and treatment of liver ischemia and reperfusion injury in mice. Am J Transplant. 2020; 21(2):540-551. PMC: 7891328. DOI: 10.1111/ajt.16269. View

10.

Scaffidi P, Misteli T, Bianchi M . Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature. 2002; 418(6894):191-5. DOI: 10.1038/nature00858. View

11.

Wu T, Zhang W, Yang G, Li H, Chen Q, Song R . HMGB1 overexpression as a prognostic factor for survival in cancer: a meta-analysis and systematic review. Oncotarget. 2016; 7(31):50417-50427. PMC: 5226592. DOI: 10.18632/oncotarget.10413. View

12.

Tang T, Wang S, Cai T, Cheng Z, Meng Y, Qi S . High mobility group box 1 regulates gastric cancer cell proliferation and migration via RAGE-mTOR/ERK feedback loop. J Cancer. 2021; 12(2):518-529. PMC: 7739007. DOI: 10.7150/jca.51049. View

13.

Faioni E, Ferrero S, Fontana G, Gianelli U, Ciulla M, Vecchi M . Expression of endothelial protein C receptor and thrombomodulin in the intestinal tissue of patients with inflammatory bowel disease. Crit Care Med. 2004; 32(5 Suppl):S266-70. DOI: 10.1097/01.ccm.0000128032.85396.83. View

14.

Scheeren F, Kuo A, van Weele L, Cai S, Glykofridis I, Sikandar S . A cell-intrinsic role for TLR2-MYD88 in intestinal and breast epithelia and oncogenesis. Nat Cell Biol. 2014; 16(12):1238-48. DOI: 10.1038/ncb3058. View

15.

Sowinska A, Rensing M, Klevenvall L, Neog M, Lundback P, Harris H . Cleavage of HMGB1 by Proteolytic Enzymes Associated with Inflammatory Conditions. Front Immunol. 2021; 11:448262. PMC: 7772184. DOI: 10.3389/fimmu.2020.448262. View

16.

. Japanese gastric cancer treatment guidelines 2018 (5th edition). Gastric Cancer. 2020; 24(1):1-21. PMC: 7790804. DOI: 10.1007/s10120-020-01042-y. View

17.

Pontarollo G, Melzow F, Reinhardt C . Comment on "Endothelial Protein C Receptor (EPCR), Protease Activated Receptor-1 (PAR-1) and Their Interplay in Cancer Growth and Metastatic Dissemination" 2019, , 51. Cancers (Basel). 2019; 11(3). PMC: 6468748. DOI: 10.3390/cancers11030374. View

18.

Liu W, Li C, Cheng W, Chang C, Chen Y, Lu C . High Mobility Group Box 1 Promotes Lung Cancer Cell Migration and Motility via Regulation of Dynamin-Related Protein 1. Int J Mol Sci. 2021; 22(7). PMC: 8036886. DOI: 10.3390/ijms22073628. View

19.

Yang G, Zhang L, Bo J, Huo X, Chen H, Cao M . Increased expression of HMGB1 is associated with poor prognosis in human bladder cancer. J Surg Oncol. 2012; 106(1):57-61. DOI: 10.1002/jso.23040. View

20.

Chung H, Jang S, Kim H, Lim J . Combined targeting of high-mobility group box-1 and interleukin-8 to control micrometastasis potential in gastric cancer. Int J Cancer. 2015; 137(7):1598-609. DOI: 10.1002/ijc.29539. View