HMGB1 suppresses colon carcinoma cell apoptosis triggered by co‑culture with dendritic cells via an ER stress‑associated autophagy pathway

Zheng,Yingcheng; Zhu,Guoguo

doi:10.3892/mmr.2017.8202

HMGB1 suppresses colon carcinoma cell apoptosis triggered by co‑culture with dendritic cells via an ER stress‑associated autophagy pathway

Authors:
- Yingcheng Zheng
- Guoguo Zhu
View Affiliations

Affiliations: Department of Infection Control, Wuhan General Hospital of Guangzhou Command, Wuhan, Hubei 430070, P.R. China, Department of Emergency and Critical Care Medicine, Wuhan General Hospital of Guangzhou Command, Wuhan, Hubei 430070, P.R. China
Published online on: December 6, 2017 https://doi.org/10.3892/mmr.2017.8202
Pages: 3123-3132

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

High mobility group box protein 1 (HMGB1) is a versatile molecule that affects the immune system in various ways; however, its role in cancer immunity has not yet been completely elucidated. In the current study, bone marrow‑derived dendritic cells from BALB/c mice and undifferentiated murine colon carcinoma CT26.WT cells were used as a cellular model to study the primary role of HMGB1 in colon cancer immunity. Annexin V and acridine orange/ethidium bromide staining was used to assess cellular apoptosis, Cell Counting kit 8 and lactate dehydrogenase assays were performed to evaluate cell viability and a monodansylcadaverine assay was used to detect autophagy. Western blot analysis was performed to detect the expression levels of proteins of interest. Endoplasmic reticulum (ER) stress and c‑Jun N‑terminal kinase phosphorylation were also investigated in CT26.WT cells exposed to dendritic cells. The present results demonstrated that the CT26.WT cells underwent apoptotic cell death following co‑culturing with dendritic cells. However, pretreatment with HMGB1 resulted in a significant increase in viability of the CT26.WT cells exposed to dendritic cells. Furthermore, HMGB1 promoted ER stress‑induced autophagy through the activation of JNK, which inhibited the apoptosis triggered by the dendritic cells, suggesting that HMGB1 has a role in immune evasion by colon cancer cells.

View Figures

View References

1	Engblom C, Pfirschke C and Pittet MJ: The role of myeloid cells in cancer therapies. Nat Rev Cancer. 16:447–462. 2016. View Article : Google Scholar : PubMed/NCBI
2	Banchereau J and Steinman RM: Dendritic cells and the control of immunity. Nature. 392:245–252. 1998. View Article : Google Scholar : PubMed/NCBI
3	James BR, Brincks EL, Kucaba TA, Boon L and Griffith TS: Effective TRAIL-based immunotherapy requires both plasmacytoid and CD8α dendritic cells. Cancer Immunol Immunother. 63:685–697. 2014. View Article : Google Scholar : PubMed/NCBI
4	Oppenheim JJ and Yang D: Alarmins: Chemotactic activators of immune responses. Curr Opin Immunol. 17:359–365. 2005. View Article : Google Scholar : PubMed/NCBI
5	Chiba S, Baghdadi M, Akiba H, Yoshiyama H, Kinoshita I, Dosaka-Akita H, Fujioka Y, Ohba Y, Gorman JV, Colgan JD, et al: Tumor-infiltrating DCs suppress nucleic acid-mediated innate immune responses through interactions between the receptor TIM-3 and the alarmin HMGB1. Nat Immunol. 13:832–842. 2012. View Article : Google Scholar : PubMed/NCBI
6	Scaffidi P, Misteli T and Bianchi ME: Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature. 418:191–195. 2002. View Article : Google Scholar : PubMed/NCBI
7	Tang D, Kang R, Zeh HJ III and Lotze MT: High-mobility group box 1 and cancer. Biochim Biophys Acta. 1799:131–140. 2010. View Article : Google Scholar : PubMed/NCBI
8	Martinotti S, Patrone M and Ranzato E: Emerging roles for HMGB1 protein in immunity, inflammation, and cancer. Immunotargets Ther. 4:101–109. 2015.PubMed/NCBI
9	Tang D, Kang R, Livesey KM, Cheh CW, Farkas A, Loughran P, Hoppe G, Bianchi ME, Tracey KJ, Zeh HJ III and Lotze MT: Endogenous HMGB1 regulates autophagy. J Cell Biol. 190:881–892. 2010. View Article : Google Scholar : PubMed/NCBI
10	Campana L, Bosurgi L and Rovere-Querini P: HMGB1: A two-headed signal regulating tumor progression and immunity. Curr Opin Immunol. 20:518–523. 2008. View Article : Google Scholar : PubMed/NCBI
11	Levine B and Kroemer G: Autophagy in the pathogenesis of disease. Cell. 132:27–42. 2008. View Article : Google Scholar : PubMed/NCBI
12	Mizushima N, Levine B, Cuervo AM and Klionsky DJ: Autophagy fights disease through cellular self-digestion. Nature. 451:1069–1075. 2008. View Article : Google Scholar : PubMed/NCBI
13	Kondo Y, Kanzawa T, Sawaya R and Kondo S: The role of autophagy in cancer development and response to therapy. Nat Rev Cancer. 5:726–734. 2005. View Article : Google Scholar : PubMed/NCBI
14	White E and DiPaola RS: The double-edged sword of autophagy modulation in cancer. Clin Cancer Res. 15:5308–5316. 2009. View Article : Google Scholar : PubMed/NCBI
15	Ogata M, Hino S, Saito A, Morikawa K, Kondo S, Kanemoto S, Murakami T, Taniguchi M, Tanii I, Yoshinaga K, et al: Autophagy is activated for cell survival after endoplasmic reticulum stress. Mol Cell Biol. 26:9220–9231. 2006. View Article : Google Scholar : PubMed/NCBI
16	Hoyer-Hansen M and Jäättelä M: Connecting endoplasmic reticulum stress to autophagy by unfolded protein response and calcium. Cell Death Differ. 14:1576–1582. 2007. View Article : Google Scholar : PubMed/NCBI
17	Li C, Capan E, Zhao Y, Zhao J, Stolz D, Watkins SC, Jin S and Lu B: Autophagy is induced in CD4+ T cells and important for the growth factor-withdrawal cell death. J Immunol. 177:5163–5168. 2006. View Article : Google Scholar : PubMed/NCBI
18	Kang R, Zeh HJ, Lotze MT and Tang D: The Beclin 1 network regulates autophagy and apoptosis. Cell Death Differ. 18:571–580. 2011. View Article : Google Scholar : PubMed/NCBI
19	Kang R, Livesey KM, Zeh HJ, Loze MT and Tang D: HMGB1: A novel Beclin 1-binding protein active in autophagy. Autophagy. 6:1209–1211. 2010. View Article : Google Scholar : PubMed/NCBI
20	Lutz MB, Kukutsch N, Ogilvie AL, Rössner S, Koch F, Romani N and Schuler G: An advanced culture method for generating large quantities of highly pure dendritic cells from mouse bone marrow. J Immunol Methods. 223:77–92. 1999. View Article : Google Scholar : PubMed/NCBI
21	Khong HT and Restifo NP: Natural selection of tumor variants in the generation of ‘tumor escape’ phenotypes. Nat Immunol. 3:999–1005. 2002. View Article : Google Scholar : PubMed/NCBI
22	Steinman RM and Banchereau J: Taking dendritic cells into medicine. Nature. 449:419–426. 2007. View Article : Google Scholar : PubMed/NCBI
23	Banchereau J and Palucka AK: Dendritic cells as therapeutic vaccines against cancer. Nat Rev Immunol. 5:296–306. 2005. View Article : Google Scholar : PubMed/NCBI
24	Kim R, Emi M and Tanabe K: Cancer immunoediting from immune surveillance to immune escape. Immunology. 121:1–14. 2007. View Article : Google Scholar : PubMed/NCBI
25	Liu L, Yang M, Kang R, Wang Z, Zhao Y, Yu Y, Xie M, Yin X, Livesey KM, Lotze MT, et al: HMGB1-induced autophagy promotes chemotherapy resistance in leukemia cells. Leukemia. 25:23–31. 2011. View Article : Google Scholar : PubMed/NCBI
26	Tang D and Lotze MT: Tumor immunity times out: TIM-3 and HMGB1. Nat Immunol. 13:808–810. 2012. View Article : Google Scholar : PubMed/NCBI
27	Kusume A, Sasahira T, Luo Y, Isobe M, Nakagawa N, Tatsumoto N, Fujii K, Ohmori H and Kuniyasu H: Suppression of dendritic cells by HMGB1 is associated with lymph node metastasis of human colon cancer. Pathobiology. 76:155–162. 2009. View Article : Google Scholar : PubMed/NCBI