N-myc Downstream-regulated Gene 1 Promotes Tumor Inflammatory Angiogenesis Through JNK Activation and Autocrine Loop of Interleukin-1α by Human Gastric Cancer Cells

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2013 Jul 13

PMID 23846687

Citations 26

Authors

Yuichi Murakami

Kosuke Watari

Tomohiro Shibata

Manami Uba

Hiroki Ureshino

Akihiko Kawahara

Hideyuki Abe

Hiroto Izumi

Naofumi Mukaida

Michihiko Kuwano

Mayumi Ono

Affiliations

Soon will be listed here.

Abstract

The expression of N-myc downstream-regulated gene 1 (NDRG1) was significantly correlated with tumor angiogenesis and malignant progression together with poor prognosis in gastric cancer. However, the underlying mechanism for the role of NDRG1 in the malignant progression of gastric cancer remains unknown. Here we examined whether and how NDRG1 could modulate tumor angiogenesis by human gastric cancer cells. We established NU/Cap12 and NU/Cap32 cells overexpressing NDRG1 in NUGC-3 cells, which show lower tumor angiogenesis in vivo. Compared with parental NU/Mock3, NU/Cap12, and NU/Cap32 cells: 1) induced higher tumor angiogenesis than NU/Mock3 cells accompanied by infiltration of tumor-associated macrophages in mouse dorsal air sac assay and Matrigel plug assay; 2) showed much higher expression of CXC chemokines, MMP-1, and the potent angiogenic factor VEGF-A; 3) increased the expression of the representative inflammatory cytokine, IL-1α; 4) augmented JNK phosphorylation and nuclear expression of activator protein 1 (AP-1). Further analysis demonstrated that knockdown of AP-1 (Jun and/or Fos) resulted in down-regulation of the expression of VEGF-A, CXC chemokines, and MMP-1, and also suppressed expression of IL-1α in NDRG1-overexpressing cell lines. Treatment with IL-1 receptor antagonist (IL-1ra) resulted in down-regulation of JNK and c-Jun phosphorylation, and the expression of VEGF-A, CXC chemokines, and MMP-1 in NU/Cap12 and NU/Cap32 cells. Finally, administration of IL-1ra suppressed both tumor angiogenesis and infiltration of macrophages by NU/Cap12 in vivo. Together, activation of JNK/AP-1 thus seems to promote tumor angiogenesis in relationship to NDRG1-induced inflammatory stimuli by gastric cancer cells.

Citing Articles

The epithelial adherens junction component PLEKHA7 regulates ECM remodeling and cell behavior through miRNA-mediated regulation of MMP1 and LOX.

Daulagala A, Cetin M, Nair-Menon J, Jimenez D, Bridges M, Bradshaw A bioRxiv. 2024; .

PMID: 38853930 PMC: 11160653. DOI: 10.1101/2024.05.28.596237.

N-myc downstream-regulated gene 1 can promote vasculogenic mimicry and angiogenesis in urothelial carcinoma.

Louis E, Abdelkawi I, Refaiy A, Ahmed A Virchows Arch. 2024; 484(5):827-836.

PMID: 38561462 PMC: 11106159. DOI: 10.1007/s00428-024-03793-w.

Induced by Direct Interaction between Esophageal Squamous Cell Carcinomas and Macrophages Promotes Tumor Progression via Secretion of IL-1α.

Azumi Y, Koma Y, Tsukamoto S, Kitamura Y, Ishihara N, Yamanaka K Cells. 2023; 12(22).

PMID: 37998338 PMC: 10670642. DOI: 10.3390/cells12222603.

The Interaction between Macrophages and Triple-negative Breast Cancer Cells Induces ROS-Mediated Interleukin 1α Expression to Enhance Tumorigenesis and Metastasis.

Hao M, Huang B, Wu R, Peng Z, Luo K Adv Sci (Weinh). 2023; 10(29):e2302857.

PMID: 37551997 PMC: 10582438. DOI: 10.1002/advs.202302857.

Re-Shaping the Pancreatic Cancer Tumor Microenvironment: A New Role for the Metastasis Suppressor NDRG1.

Chang J, Lo Z, Alenizi S, Kovacevic Z Cancers (Basel). 2023; 15(10).

PMID: 37345116 PMC: 10216318. DOI: 10.3390/cancers15102779.

References

Nakao S, Kuwano T, Tsutsumi-Miyahara C, Ueda S, Kimura Y, Hamano S . Infiltration of COX-2-expressing macrophages is a prerequisite for IL-1 beta-induced neovascularization and tumor growth. J Clin Invest. 2005; 115(11):2979-91. PMC: 1257532. DOI: 10.1172/JCI23298. View

Watari K, Nakao S, Fotovati A, Basaki Y, Hosoi F, Bereczky B . Role of macrophages in inflammatory lymphangiogenesis: Enhanced production of vascular endothelial growth factor C and D through NF-kappaB activation. Biochem Biophys Res Commun. 2008; 377(3):826-31. DOI: 10.1016/j.bbrc.2008.10.077. View

Apte R, Voronov E . Is interleukin-1 a good or bad 'guy' in tumor immunobiology and immunotherapy?. Immunol Rev. 2008; 222:222-41. DOI: 10.1111/j.1600-065X.2008.00615.x. View

Finkenzeller G, Technau A, Marme D . Hypoxia-induced transcription of the vascular endothelial growth factor gene is independent of functional AP-1 transcription factor. Biochem Biophys Res Commun. 1995; 208(1):432-9. DOI: 10.1006/bbrc.1995.1356. View

Song Y, Oda Y, Hori M, Kuroiwa K, Ono M, Hosoi F . N-myc downstream regulated gene-1/Cap43 may play an important role in malignant progression of prostate cancer, in its close association with E-cadherin. Hum Pathol. 2009; 41(2):214-22. DOI: 10.1016/j.humpath.2009.07.011. View

Kimura Y, Watari K, Fotovati A, Hosoi F, Yasumoto K, Izumi H . Inflammatory stimuli from macrophages and cancer cells synergistically promote tumor growth and angiogenesis. Cancer Sci. 2007; 98(12):2009-18. PMC: 11159678. DOI: 10.1111/j.1349-7006.2007.00633.x. View

Chua M, Sun H, Cheung S, Mason V, Higgins J, Ross D . Overexpression of NDRG1 is an indicator of poor prognosis in hepatocellular carcinoma. Mod Pathol. 2006; 20(1):76-83. DOI: 10.1038/modpathol.3800711. View

Chen Z, Zhang D, Yue F, Zheng M, Kovacevic Z, Richardson D . The iron chelators Dp44mT and DFO inhibit TGF-β-induced epithelial-mesenchymal transition via up-regulation of N-Myc downstream-regulated gene 1 (NDRG1). J Biol Chem. 2012; 287(21):17016-17028. PMC: 3366822. DOI: 10.1074/jbc.M112.350470. View

Murray J, Campbell D, Morrice N, Auld G, Shpiro N, Marquez R . Exploitation of KESTREL to identify NDRG family members as physiological substrates for SGK1 and GSK3. Biochem J. 2004; 384(Pt 3):477-88. PMC: 1134133. DOI: 10.1042/BJ20041057. View

10.

Murakami Y, Hosoi F, Izumi H, Maruyama Y, Ureshino H, Watari K . Identification of sites subjected to serine/threonine phosphorylation by SGK1 affecting N-myc downstream-regulated gene 1 (NDRG1)/Cap43-dependent suppression of angiogenic CXC chemokine expression in human pancreatic cancer cells. Biochem Biophys Res Commun. 2010; 396(2):376-81. DOI: 10.1016/j.bbrc.2010.04.100. View

11.

Guadagni S, De Manzoni G, Catarci M, Valenti M, Amicucci G, De Bernardinis G . Evaluation of the Maruyama computer program accuracy for preoperative estimation of lymph node metastases from gastric cancer. World J Surg. 2001; 24(12):1550-8. DOI: 10.1007/s002680010276. View

12.

Sohda M, Mochida Y, Kato H, Miyazaki T, Nakajima M, Fukuchi M . Overexpression of Cap43 is associated with malignant status of esophageal cancer. Anticancer Res. 2009; 29(4):965-70. View

13.

Ishikawa Y, Mukaida N, Kuno K, Rice N, Okamoto S, Matsushima K . Establishment of lipopolysaccharide-dependent nuclear factor kappa B activation in a cell-free system. J Biol Chem. 1995; 270(8):4158-64. View

14.

Fukahori S, Yano H, Tsuneoka M, Tanaka Y, Yagi M, Kuwano M . Immunohistochemical expressions of Cap43 and Mina53 proteins in neuroblastoma. J Pediatr Surg. 2007; 42(11):1831-40. DOI: 10.1016/j.jpedsurg.2007.07.008. View

15.

Yoshida S, Ono M, Shono T, Izumi H, Ishibashi T, Suzuki H . Involvement of interleukin-8, vascular endothelial growth factor, and basic fibroblast growth factor in tumor necrosis factor alpha-dependent angiogenesis. Mol Cell Biol. 1997; 17(7):4015-23. PMC: 232254. DOI: 10.1128/MCB.17.7.4015. View

16.

Qian B, Pollard J . Macrophage diversity enhances tumor progression and metastasis. Cell. 2010; 141(1):39-51. PMC: 4994190. DOI: 10.1016/j.cell.2010.03.014. View

17.

Carmi Y, Voronov E, Dotan S, Lahat N, Rahat M, Fogel M . The role of macrophage-derived IL-1 in induction and maintenance of angiogenesis. J Immunol. 2009; 183(7):4705-14. DOI: 10.4049/jimmunol.0901511. View

18.

Maruyama Y, Ono M, Kawahara A, Yokoyama T, Basaki Y, Kage M . Tumor growth suppression in pancreatic cancer by a putative metastasis suppressor gene Cap43/NDRG1/Drg-1 through modulation of angiogenesis. Cancer Res. 2006; 66(12):6233-42. DOI: 10.1158/0008-5472.CAN-06-0183. View

19.

Tu S, Bhagat G, Cui G, Takaishi S, Kurt-Jones E, Rickman B . Overexpression of interleukin-1beta induces gastric inflammation and cancer and mobilizes myeloid-derived suppressor cells in mice. Cancer Cell. 2008; 14(5):408-19. PMC: 2586894. DOI: 10.1016/j.ccr.2008.10.011. View

20.

Bandyopadhyay S, Pai S, Hirota S, Hosobe S, Takano Y, Saito K . Role of the putative tumor metastasis suppressor gene Drg-1 in breast cancer progression. Oncogene. 2004; 23(33):5675-81. DOI: 10.1038/sj.onc.1207734. View