Articles

The Effect of Recombinant HopH Protein of Helicobacter pylori on the VEGF Expression in Metastatic Breast Cancer Model

Abstract

Breast cancer imposes a considerable amount of cancer-related mortality and morbidity among women worldwide. Many efforts are in progress to reduce the disease burden and amongst the bacterial-based products received considerable attention as potential anti-cancer drugs. In the present study, the effect of recombinant pro-inflammatory outer membrane protein (HopH) of Helicobacter pylori on the angiogenic factor and tumor development in metastatic breast cancer model was evaluated. The HopH gene was cloned into Pet28a vector, induced by IPTG and expressed and purified by Ni-NTA affinity chromatography. The expressed protein was confirmed by SDS-page. The breast cancer tumor induction was performed using Breast cancer cell line (4T1). The mice were divided into different groups and underwent treatment by recombinant HopH and Herceptin, subsequently. The treatment effectiveness on tumor size was followed, and the expression level of vascular endothelial growth factor was evaluation by real time PCR. The SDS-PAGE analysis confirmed the expression of HopH protein with an approximate 34KD weight. Based on our results, the expression level of VEGF was significantly reduced in HopH-treated mice group comparing to the control and Herceptin group. Our results have shown that the recombinant HopH protein can effectively reduce VEGF expression in breast cancer tumor which was associated with reduction of tumor size. The HopH protein can be considered as a potential anti-cancer agent for future cancer therapeutic studies.

Cejalvo JM, Martínez de Dueñas E, Galván P, García-Recio S, Burgués Gasión O, et al. Intrinsic Subtypes and Gene Expression Profiles in Primary and Metastatic Breast Cancer. Cancer Res 2017;77:2213-21.

Hendrix MJ, Seftor EA, Seftor RE. Vasculogenic Mimicry: Angiogenesis in Disguise? (Accessed April 2016, 189, at https://link.springer.com/chapter/10.1007/1-4020-4327-9_5).

Klaus Unsicker K, Krieglstei K. Vasculogenesis. In: Breier G, editor. Cell Signaling and Growth Factors in Development. From Molecules to Organogenesis,

:909-24.

hey WD, Leontiadis GI, Howden CW, Moss SF. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol 2017;112:212-39.

Yamaoka Y, Kikuchi S, El–Zimaity HM, Gutierrez O, Osato MS, Graham DY. Importance ofHelicobacter pylori oipA in clinical presentation, gastric inflammation, and mucosal interleukin 8 production. Gastroenterology 2002;123:414-24.

Soleimani N, Mohabati Mobarez A. Cloning, expression and purification flagellar sheath adhesion of Helicobacter pylori in Escherichia coli host as a vaccination target. Clin Exp Vaccine Res 2016;1:19-25.

Soleimani N, Farhangi B, Mohabati Mobarez A, Etyabi F. VEGF and MMP-9 Gene Expression Caused by Treatment with Helicobacter Pylori Neutrophil-activating Recombinant Protein in a Breast Cancer Model. J Babol Univ Med Sci 2015:17:13-9.

Liu J, He C, Chen M, Wang Z, Xing C, Yuan Y. Association of presence/absence and on/off patterns of Helicobacter pylori oipA gene with peptic ulcer disease and gastric cancer risks: a meta-analysis. BMC Infect Dis 2013;13:555.

Zhang J, Qian J, Zhang X, Zou Q. Outer membrane inflammatory protein A, a new virulence factor involved in the pathogenesis of Helicobacter pylori. Mol Biol Rep 2014;41:7807-14.

Tabassam FH, Graham DY, Yamaoka Y. OipA plays a role in Helicobacter pylori-induced focal adhesion kinase activation and cytoskeletal re-organization. Cell Microbiol 2008;10:1008-20.

Shah C, Khwaja S, Badiyan S, Wilkinson JB, Vicini FA, Beitsch P, et al. Brachytherapy-based partial breast irradiation is associated with low rates of complications and excellent cosmesis. Brachytherapy 2013;12:278-84.

Bollag BM, Edelstein S, Rozicky M. Proteins methods. Jhon Wiley and Sons Pub., 1996.

Wingfield PT. Overview of the purification of recombinant proteins. Curr Protoc Protein Sci. 2015: 1;80:6.1.1-35.

Tinoco G, Warsch S, Glück S, Avancha K, Montero AJ. Treating breast cancer in the 21st century: emerging biological therapies. J Cancer 2013;4:117.

Tang C, Ang BT, Pervaiz S. Cancer stem cell: target for anti-cancer therapy. FASEB J 2007;21:3777-85.

Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CH, Jones DL, et al. Cancer stem cells—perspectives on current status and future directions: AACR Workshop on cancer stem cells. Cancer Res 2006;66:9339-44.

Dent S, Oyan B, Honig A, Mano M, Howell S. HER2-targeted therapy in breast cancer: a systematic review of neoadjuvant trials. Cancer Treat Rev 2013;39:622-s31

Hirayama T, Wada A, Yahiro K, Kimura M, Kimura T. Helicobacter pylori vacuolating cytotoxin, VacA. Japan J Infect Dis 2002;55:1-5.

Handa O, Naito Y, Yoshikawa T. CagA protein of Helicobacter pylori: A hijacker of gastric epithelial cell signaling. Biochem Ppharmacol 2007;73:1697-702 . 20. Teymournejad O, Mobarez AM, Hassan ZM, Moazzeni SM, Yakhchali B, Eskandari V. In silico prediction of exposure amino acid sequences of outer inflammatory protein A of Helicobacter pylori for surface display on Eschierchia coli, Indian J Hum Genet 2012;18:83-6.

Teymournejad O, Mobarez AM, Hassan ZM, Moazzeni SM, Ahmadabad HN. In Vitro Suppression of Dendritic Cells by Helicobacter pylori OipA. Helicobacter 2014;19:136-43.

Soleimani N, Mohabati-Mobarez A, Atyabi F, Hasan-Saraf Z, Haghighi MA. Preparation of chitosan nanoparticles carrying recombinant helicobacter pylori neutrophil-activating protein. J Mazandaran Univ Med Sci 2014;23:134-44.

Nakamura Y, Yasuoka H, Tsujimoto M, Yoshidome K, Nakahara M, Nakao K, et al. Nitric oxide in breast cancer: induction of vascular endothelial growth factor-C and correlation with metastasis and poor prognosis. Clin Cancer Res 2006;12:1201-7.

Ghattass K, El-Sitt S, Zibara K, Rayes S, Haddadin MJ, El-Sabban M, et al. The quinoxaline di-N-oxide DCQ

blocks breast cancer metastasis in vitro and in vivo by targeting the hypoxia inducible factor-1 pathway. Mol Cancer 2014;13:12.

Mousavi M, Baharara J, Shahrokhabadi K, Balanejad S. .Effect of saffron extract on VEGF-A expression in MCF7 cell line. J Kermanshah Univ Med Sci 2014;17:749-58 ,

Oleastro M, Menard A. The Role of Helicobacter pylori Outer Membrane Proteins in Adherence and Pathogenesis. Biology 2013;2;1110-34.

Tabassam FH, Graham DY, Yamaoka Y. Paxillin is a novel cellular target for converging Helicobacter pylori-induced cellular signaling. Am J Physiol Gastrointest Liver Physiol 2011;301:601-11.

Chen J, Lin L, Li N, She F. Enhancement of Helicobacter pylori outer inflammatory protein DNA vaccine efficacy by co-delivery of interleukin-2 and B subunit heat-labile toxin gene encoded plasmids. Microbiol Immunol 2012;56:85-92.

De Francesco EM, Pellegrino M, Santolla MF, Lappano R, Ricchio E, Abonante S, et al. GPER mediates activation of HIF-1α/VEGF signaling by estrogens. Cancer Res 2014;74:4053-64.

Tsuboi K, Matsuo Y, Shamoto T, Shibata T, Koide S, Morimoto M, et al. Zerumbone inhibits tumor angiogenesis via NF-κB in gastric cancer. Oncol Rep 2014;31:57-64.

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IssueVol 55, No 12 (2017) QRcode
SectionArticles
Keywords
HopH Breast cancer Metastasis

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How to Cite
1.
Soleimani N, Farhangi B, Tavakoli Yaraki M. The Effect of Recombinant HopH Protein of Helicobacter pylori on the VEGF Expression in Metastatic Breast Cancer Model. Acta Med Iran. 2018;55(12):744-750.