Aberrant expression of IL-23/IL-23R in patients with breast cancer and its clinical significance

Sheng,Shuhai; Zhang,Jinji; Ai,Jianzhong; Hao,Xueli; Luan,Ruishen

doi:10.3892/mmr.2018.8427

Aberrant expression of IL-23/IL-23R in patients with breast cancer and its clinical significance

Authors:
- Shuhai Sheng
- Jinji Zhang
- Jianzhong Ai
- Xueli Hao
- Ruishen Luan
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Affiliations: Department of Breast Cancer Surgery, Tangshan Gongren Hospital, Tangshan, Hebei 063000, P.R. China, North China University of Science and Technology Affiliated Hospital, Tangshan, Hebei 063000, P.R. China, Department of Oncological Surgery, Tangshan Gongren Hospital, Tangshan, Hebei 063000, P.R. China, Department of Breast and Neck Surgery, The Third Hospital of Chengde City, Chengde, Hebei 067000, P.R. China
Published online on: January 12, 2018 https://doi.org/10.3892/mmr.2018.8427
Pages: 4639-4644

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Abstract

Breast cancer tissues and adjacent tissues were collected from 32 patients who were treated in The Third Hospital of Chengde City. Reverse transcription‑quantitative polymerase chain reaction results demonstrated that, compared with the adjacent tissues, interleukin (IL)‑23/IL‑23 receptor (R) gene expression levels were notably higher in breast cancer tissues. Furthermore, IL‑23 and IL‑23R expression levels were positively correlated with patients' tumor size, TNM stage and metastasis. Recombinant human (rh) IL‑23 (10 ng/ml) was used for the stimulation of the MCF‑7 cell line. Effects of rh IL‑23 (10 ng/ml) on cell proliferation was detected after MCF‑7 cells were incubated with rh IL‑23 for 48 h. Whether pre‑treatment with polyclonal antibody (PAb) IL‑23p19, a neutralizing antibody specific for IL‑23, may influence the effects of IL‑23 on cell behavior was also investigated. Cell proliferation assay and cell apoptosis assay were evaluated using MTT assay and flow cytometry assay, respectively. Results suggested that PAb IL‑23p19 reduced IL-23-induced cell proliferation whereas induced IL‑23 inhibited cell apoptosis. Western blot analysis was performed for the detection of molecules that may be responsible for the aforementioned changes. Results indicated that PAb IL‑23p19 treatment reduced IL‑23‑induced upregulation of B‑cell lymphoma‑2 protein expression and activation of the janus kinase 2/signal transducer and activator of transcription 3 signaling pathway. The present results suggested that IL‑23 may be a potential prognosis marker and target for the treatment of breast cancer patients.

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1	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar : PubMed/NCBI
2	Jemal A, Siegel R, Xu J and Ward E: Cancer statistics, 2010. Cancer J Clin. 60:277–300. 2010. View Article : Google Scholar
3	Cardoso F, Harbeck N, Barrios CH, Bergh J, Cortés J, EI Saghir N, Francis PA, Hudis CA, Ohno S, Partridge AH, et al: Research needs in breast cancer. Ann Oncol. 28:208–217. 2017.PubMed/NCBI
4	Harbeck N and Gnant M: Breast cancer. Lancet. 389:1134–1150. 2017. View Article : Google Scholar : PubMed/NCBI
5	Ahern PP, Izcue A, Maloy KJ and Powrie F: The interleukin-23 axis in intestinal inflammation. Immunol Rev. 226:147–159. 2008. View Article : Google Scholar : PubMed/NCBI
6	Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, McClanahan T, Kastelein RA and Cua DJ: IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med. 201:233–240. 2005. View Article : Google Scholar : PubMed/NCBI
7	Lee E, Trepicchio WL, Oestreicher JL, Pittman D, Wang F, Chamian F, Dhodapkar M and Krueger JG: Increased expression of interleukin 23 p19 and p40 in lesional skin of patients with psoriasis vulgaris. J Exp Med. 199:125–130. 2004. View Article : Google Scholar : PubMed/NCBI
8	Chen Z, Laurence A and O'Shea JJ: Signal transduction pathways and transcriptional regulation in the control of Th17 differentiation. Semin Immunol. 19:400–408. 2007. View Article : Google Scholar : PubMed/NCBI
9	Volpe E, Servant N, Zollinger R, Bogiatzi SI, Hupé P, Barillot E and Soumelis V: A critical function for transforming growth factorbeta, interleukin 23 and proinflammatory cytokines in driving and modulating human T(H)-17 responses. Nat Immunol. 9:650–657. 2008. View Article : Google Scholar : PubMed/NCBI
10	Cho JH and Weaver CT: The genetics of inflammatory bowel disease. Gastroenterology. 133:1327–1339. 2007. View Article : Google Scholar : PubMed/NCBI
11	Le Gouvello S, Bastuji-Garin S, Aloulou N, Mansour H, Chaumette MT, Berrehar F, Seikour A, Charachon A, Karoui M, Leroy K, et al: High prevalence of Foxp3 and IL17 in MMR proficient colorectal carcinomas. Gut. 57:772–779. 2008. View Article : Google Scholar : PubMed/NCBI
12	Langowski JL, Zhang X, Wu L, Mattson JD, Chen T, Smith K, Basham B, McClanahan T, Kastelein RA and Oft M: IL-23 promotes tumor incidence and growth. Nature. 442:461–465. 2006. View Article : Google Scholar : PubMed/NCBI
13	Balkwill F and Mantovani A: Inflammation and cancer: Back to Virchow? Lancet. 357:539–545. 2001. View Article : Google Scholar : PubMed/NCBI
14	Fukuda M, Ehara M, Suzuki S and Sakashita H: Expression of interleukin-23 and its receptors in human squamous cell carcinoma of the oral cavity. Mol Med Rep. 3:89–93. 2010.PubMed/NCBI
15	Gangemi S, Minciullo P, Adamo B, Franchina T, Ricciardi GR, Ferraro M, Briguglio R, Toscano G, Saitta S and Adamo V: Clinical significance of circulating interleukin-23 as a prognostic factor in breast cancer patients. J Cell Biochem. 113:2122–2125. 2012. View Article : Google Scholar : PubMed/NCBI
16	Xu Y, Liu Y, Pan S, Liu L, Liu J, Zhai X, Shen H and Hu Z: IL-23R polymorphisms, HBV infection and risk of hepatocellular carcinoma in a high-risk Chinese population. J Gastroenterol. 48:125–131. 2013. View Article : Google Scholar : PubMed/NCBI
17	Wang Q, Zhou J, Zhang B, Tian Z, Tang J, Zheng Y, Huang Z, Tian Y, Jia Z, Tang Y, et al: Hepatitis B virus induces IL-23 production in antigen presenting cells and causes liver damage via the IL-23/IL-17 axis. PLoS Pathog. 9:e10034102013. View Article : Google Scholar : PubMed/NCBI
18	Yu H, Kortylewski M and Pardoll D: Crosstalk between cancer and immune cells: Role of STAT3 in the tumour microenvironment. Nat Rev Immunol. 7:41–51. 2007. View Article : Google Scholar : PubMed/NCBI
19	Coussens LM and Werb Z: Inflammation and cancer. Nature. 420:860–867. 2002. View Article : Google Scholar : PubMed/NCBI
20	Balkwill F, Charles KA and Mantovani A: Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell. 7:211–217. 2005. View Article : Google Scholar : PubMed/NCBI
21	Parham C, Chirica M, Timans J, Vaisberg E, Travis M, Cheung J, Pflanz S, Zhang R, Singh KP, Vega F, et al: A receptor for the heterodi-meric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R. J Immunol. 168:5699–5708. 2002. View Article : Google Scholar : PubMed/NCBI
22	Aaronson DS and Horvath CM: A road map for those who don't know JAK-STAT. Science. 296:1653–1655. 2002. View Article : Google Scholar : PubMed/NCBI
23	Hebenstreit D, Horejs-Hoeck J and Duschl A: JAK/STAT-dependent gene regulation by cytokines. Drug News Perspect. 18:243–249. 2005. View Article : Google Scholar : PubMed/NCBI
24	Marotta LL, Almendro V, Marusyk A, Shipitsin M, Schemme J, Walker SR, Bloushtain-Qimron N, Kim JJ, Choudhury SA, Maruyama R, et al: The JAK2/STAT3 signaling pathway is required for growth of CD44⁺CD24 stem cell-like breast cancer cells in human tumors. J Clin Invest. 121:2723–2735. 2011. View Article : Google Scholar : PubMed/NCBI
25	Hennessy BT, Gonzalez-Angulo AM, Stemke-Hale K, Gilcrease MZ, Krishnamurthy S, Lee JS, Fridlyand J, Sahin A, Agarwal R, Joy C, et al: Characterization of a naturally occurring breast cancer subset enriched in epithelial-to-mesenchymal transition and stem cell characteristics. Cancer Res. 69:4116–4124. 2009. View Article : Google Scholar : PubMed/NCBI