Article Data

  • Views 894
  • Dowloads 132

Original Research

Open Access

Recombinant human IL-17D promotes the progression of human ovarian cancer SKOV3 cells and the expression of PD-L by activating the NF-κB pathway

  • Yuanchun Fan1
  • Lei Feng1
  • Yueping Liu2
  • Shihao Liu1
  • Hui Zhang1,*,

1The Gynecology Department, the Fourth Hospital of Hebei Medical University, 050011 Shijiazhuang, Hebei, China

2The Pathology Department, the Fourth Hospital of Hebei Medical University, 050011 Shijiazhuang, Hebei, China

DOI: 10.22514/ejgo.2024.004 Vol.45,Issue 1,February 2024 pp.17-25

Submitted: 02 August 2022 Accepted: 08 December 2022

Published: 15 February 2024

*Corresponding Author(s): Hui Zhang E-mail: zhanghui@hebmu.edu.cn

Abstract

Ovarian cancer (OC) is often diagnosed in its advanced stages with many patients suffering from recurrence. Relapse is frequent after standard treatment leading to platinum resistance and poor prognosis in patients. Several studies have reported that immune status and inflammatory factors, such as Interleukin-17D (IL-17D), are major players in the prognosis of malignant tumors. IL-17 family is an important pro-inflammatory cytokine family, which mediates immunosuppression and promotes tumor progression. Our previous exploration revealed the promoting role of IL-17D expression in the occurrence and development of ovarian carcinoma, but the specific mechanism remains unclear. In this study, we investigated the effects of rhIL-17D on the proliferation, migration and invasion of human ovarian carcinoma cell SKOV3 in vitro. In addition, we also detected the effect of rhIL-17D on programmed death ligand-1 (PD-L1) expression of SKOV3 cells and possible mechanism.We found that rhIL-17D accelerated SKOV3 cell proliferation rate, enhanced the migration and penetration ability, and promoted the expression of PD-L1. After knockdown P65 expression,the activated form of NF-κB, in SKOV3 cells, the proliferation activity, migration, and invasion of ovarian cancer cells were significantly reduced. And the expression of PD-L1 decreased. In summary, we believe that IL-17D can accelerate cell proliferation and enhance cell migration and invasion abilities of ovarian cancer and induce PD-L1 expression by regulating the activation of NF-κB pathway. Down-regulation of IL-17D in tumor microenvironment may be a new approach to inhibit ovarian cancer.


Keywords

Ovarian cancer; IL-17D; NF-κB signaling pathway; p65; PD-L1


Cite and Share

Yuanchun Fan,Lei Feng,Yueping Liu,Shihao Liu,Hui Zhang. Recombinant human IL-17D promotes the progression of human ovarian cancer SKOV3 cells and the expression of PD-L by activating the NF-κB pathway. European Journal of Gynaecological Oncology. 2024. 45(1);17-25.

References

[1] Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA: A Cancer Journal for Clinicians. 2022; 72: 7–33.

[2] Sabol M, Calleja-Agius J, Di Fiore R, Suleiman S, Ozcan S, Ward MP, et al. (In)distinctive role of long non-coding RNAs in common and rare ovarian cancers. Cancers. 2021; 13: 5040.

[3] Kuroki L, Guntupalli SR. Treatment of epithelial ovarian cancer. BMJ. 2020; 371: 3773.

[4] Hamanishi J, Mandai M, Matsumura N, Abiko K, Baba T, Konishi I. PD-1/PD-L1 blockade in cancer treatment: perspectives and issues. International Journal of Clinical Oncology. 2016; 21: 462–473.

[5] Gentzler R, Hall R, Kunk PR, Gaughan E, Dillon P, Slingluff CL, et al. Beyond melanoma: inhibiting the PD-1/PD-L1 pathway in solid tumors. Immunotherapy. 2016; 8: 583–600.

[6] Gevensleben H, Dietrich D, Golletz C, Steiner S, Jung M, Thiesler T, et al. The immune checkpoint regulator PD-L1 is highly expressed in aggressive primary prostate cancer. Clinical Cancer Research. 2016; 22: 1969–1977.

[7] Moehler M, Delic M, Goepfert K, Aust D, Grabsch HI, Halama N, et al. Immunotherapy in gastrointestinal cancer: recent results, current studies and future perspectives. European Journal of Cancer. 2016; 59: 160–170.

[8] Gainor JF. Adjuvant PD-L1 blockade in non-small-cell lung cancer. The Lancet. 2021; 398: 1281–1283.

[9] Choueiri TK, Fay AP, Gray KP, Callea M, Ho TH, Albiges L, et al. PD-L1 expression in nonclear-cell renal cell carcinoma. Annals of Oncology. 2014; 25: 2178–2184.

[10] Olino K, Park T, Ahuja N. Exposing hidden targets: combining epigenetic and immunotherapy to overcome cancer resistance. Seminars in Cancer Biology. 2020; 65: 114–122.

[11] Chen X, Zhang Q, Luo Y, Gao C, Zhuang X, Xu G, et al. High-dose irradiation in combination with toll-like receptor 9 agonist CpG oligodeoxynucleotide 7909 downregulates PD-L1 expression via the NF-κB signaling pathway in non-small cell lung cancer cells. OncoTargets and Therapy. 2016; 9: 6511–6518.

[12] Greten FR, Grivennikov SI. Inflammation and cancer: triggers, mechanisms, and consequences. Immunity. 2019; 51: 27–41.

[13] Shalapour S, Karin M. Pas de deux: control of anti-tumor immunity by cancer-associated inflammation. Immunity. 2019; 51: 15–26.

[14] Wang X, Yang L, Huang F, Zhang Q, Liu S, Ma L, et al. Inflammatory cytokines IL-17 and TNF-α up-regulate PD-L1 expression in human prostate and colon cancer cells. Immunology Letters. 2017; 184: 7–14.

[15] Shuai C, Yang X, Pan H, Han W. Estrogen receptor downregulates expression of PD-1/PD-L1 and infiltration of CD8+ T cells by inhibiting IL-17 signaling transduction in breast cancer. Frontiers in Oncology. 2020; 10: 582863.

[16] Aotsuka A, Matsumoto Y, Arimoto T, Kawata A, Ogishima J, Taguchi A, et al. Interleukin-17 is associated with expression of programmed cell death 1 ligand 1 in ovarian carcinoma. Cancer Science. 2019; 110: 3068–3078.

[17] Zhang JL, Zhang H, Zhang LK, Hu ZX. Effect of interleukin-17D gene on the growth of xenografted tumor of human ovarian carcinoma in nude mice. Tumor. 2004; 34: 712–718.

[18] Stewart C, Ralyea C, Lockwood S. Ovarian cancer: an integrated review. Seminars in Oncology Nursing. 2019; 35: 151–156.

[19] Merritt MA, Green AC, Nagle CM, Webb PM; Australian Cancer Study (Ovarian Cancer); Australian Ovarian Cancer Study Group. Talcum powder, chronic pelvic inflammation and NSAIDs in relation to risk of epithelial ovarian cancer. International Journal of Cancer. 2008; 122: 170–176.

[20] Taniguchi K, Karin M. NF-κB, inflammation, immunity and cancer: coming of age. Nature Reviews Immunology. 2018; 18: 309–324.

[21] Li X, Bechara R, Zhao J, McGeachy MJ, Gaffen SL. IL-17 receptor-based signaling and implications for disease. Nature Immunology. 2019; 20: 1594–1602.

[22] Chin C, Chen C, Kuo H, Shi C, Hsieh MC, Kuo Y, et al. Interleukin-17 induces CC chemokine receptor 6 expression and cell migration in colorectal cancer cells. Journal of Cellular Physiology. 2015; 230: 1430–1437.

[23] Bastid J, Dejou C, Docquier A, Bonnefoy N. The emerging role of the IL-17B/IL-17RB pathway in cancer. Frontiers in Immunology. 2020; 21: 718.

[24] Saddawi-Konefka R, O’Sullivan T, Gross ET, Washington A Jr, Bui JD. Tumor-expressed IL-17D recruits NK cells to reject tumors. Oncoimmunology. 2014; 3: e954853.

[25] Saddawi-Konefka R, Seelige R, Gross ET, Levy E, Searles SC, Washington A Jr, et al. Nrf2 induces IL-17D to mediate tumor and virus surveillance. Cell Reports. 2016; 16: 2348–2358.

[26] Starnes T, Broxmeyer HE, Robertson MJ, Hromas R. Cutting edge: IL-17D, a novel member of the IL-17 family, stimulates cytokine production and inhibits hemopoiesis. The Journal of Immunology. 2002; 169: 642–646.

[27] Li YY,Zhang H,Kang S, Hu Z. Expression and significance of IL-17D and CD163 in epithelial ovarian cancer. Journal of Practical Obstetrics and Gynecology. 2018; 31: 383–387.

[28] Shergold AL, Millar R, Nibbs RJB. Understanding and overcoming the resistance of cancer to PD-1/PD-L1 blockade. Pharmacological Research. 2019; 145: 104258.

[29] Hsu J, Li C, Lai Y, Hung M. Posttranslational modifications of PD-L1 and their applications in cancer therapy. Cancer Research. 2018; 78: 6349–6353.

[30] English K, Barry FP, Field-Corbett CP, Mahon BP. IFN-gamma and TNF-alpha differentially regulate immunomodulation by murine mesenchymal stem cells. Immunology Letters. 2007; 110: 91–100.

[31] Lee SJ, Jang BC, Lee SW, Yang YI, Suh SI, Park YM, et al. Interferon regulatory factor-1 is prerequisite to the constitutive expression and IFN-gamma-induced upregulation of B7-H1 (CD274). FEBS Letters. 2006; 580: 755–762.

[32] Lv Y, Zhao Y, Wang X, Chen N, Mao F, Teng Y, et al. Increased intratumoral mast cells foster immune suppression and gastric cancer progression through TNF-α-PD-L1 pathway. Journal for Immunotherapy of Cancer. 2019; 7: 54.

[33] Li H, Xia J, Zhu F, Xi Z, Pan C, Gu L, et al. LPS promotes the expression of PD-L1 in gastric cancer cells through NF-κB activation. Journal of Cellular Biochemistry. 2018; 119: 9997–10004.

[34] Rong Q, Wang F, Guo Z, Hu Y, An S, Luo M, et al. GM-CSF mediates immune evasion via upregulation of PD-L1 expression in extranodal natural killer/T cell lymphoma. Molecular Cancer. 2021; 20: 80.

[35] Qu Q, Xie F, Huang Q, Zhang X. Membranous and cytoplasmic expression of PD-L1 in ovarian cancer cells. Cellular Physiology and Biochemistry. 2017; 43: 1893–1906.

[36] Ding X, Zhang J, Shi M, Liu D, Zhang L, Zhang R, et al. High expression level of interleukin-1β is correlated with poor prognosis and PD-1 expression in patients with lung adenocarcinoma. Clinical and Translational Oncology. 2021; 23: 35–42.

[37] Wang S, Wang G, Zhang L, Li F, Liu K, Wang Y, et al. Interleukin-17 promotes nitric oxide-dependent expression of PD-L1 in mesenchymal stem cells. Cell & Bioscience. 2020; 10: 73.

[38] Wang W, Yen M, Liu K, Hsu P, Lin M, Chen P, et al. Interleukin-25 mediates transcriptional control of PD-L1 via STAT3 in multipotent human mesenchymal stromal cells (hMSCs) to suppress Th17 responses. Stem Cell Reports. 2015; 5: 392–404.

[39] Antonangeli F, Natalini A, Garassino MC, Sica A, Santoni A, Di Rosa F. Regulation of PD-L1 expression by NF-κB in cancer. Frontiers in Immunology. 2020; 11: 584626.

[40] Pramanik KC, Makena MR, Bhowmick K, Pandey MK. Advancement of NF-κB signaling pathway: a novel target in pancreatic cancer. International Journal of Molecular Sciences. 2018; 19: 3890.

[41] Patel M, Horgan PG, McMillan DC, Edwards J. NF-κB pathways in the development and progression of colorectal cancer. Translational Research. 2018; 197: 43–56.

[42] Sokolova O, Naumann M. NF-κB signaling in gastric cancer. Toxins. 2017; 9: 119.

[43] Farhadi A, Namdari S, Chong PP, Geramizadeh B, Behzad-Behbahani A, Sekawi Z, et al. Epstein-barr virus infection is associated with the nuclear factor-kappa B p65 signaling pathway in renal cell carcinoma. BMC Urology. 2022; 22: 17.

[44] Hong L, Wang S, Li W, Wu D, Chen W. Tumor-associated macrophages promote the metastasis of ovarian carcinoma cells by enhancing CXCL16/CXCR6 expression. Pathology—Research and Practice. 2018; 214: 1345–1351.

[45] Xiaomeng F, Lei L, Jinghong A, Juan J, Qi Y, Dandan Y. Treatment with β-elemene combined with paclitaxel inhibits growth, migration, and invasion and induces apoptosis of ovarian cancer cells by activation of STAT-NF-κB pathway. Brazilian Journal of Medical and Biological Research. 2020; 53: e8885.

[46] Zhao Y, Hong L. lncRNA-PRLB confers paclitaxel resistance of ovarian cancer cells by regulating RSF1/NF-κB signaling pathway. Cancer Biotherapy & Radiopharmaceuticals. 2021; 36: 202–210.


Abstracted / indexed in

Science Citation Index Expanded (SciSearch) Created as SCI in 1964, Science Citation Index Expanded now indexes over 9,500 of the world’s most impactful journals across 178 scientific disciplines. More than 53 million records and 1.18 billion cited references date back from 1900 to present.

Biological Abstracts Easily discover critical journal coverage of the life sciences with Biological Abstracts, produced by the Web of Science Group, with topics ranging from botany to microbiology to pharmacology. Including BIOSIS indexing and MeSH terms, specialized indexing in Biological Abstracts helps you to discover more accurate, context-sensitive results.

Google Scholar Google Scholar is a freely accessible web search engine that indexes the full text or metadata of scholarly literature across an array of publishing formats and disciplines.

JournalSeek Genamics JournalSeek is the largest completely categorized database of freely available journal information available on the internet. The database presently contains 39226 titles. Journal information includes the description (aims and scope), journal abbreviation, journal homepage link, subject category and ISSN.

Current Contents - Clinical Medicine Current Contents - Clinical Medicine provides easy access to complete tables of contents, abstracts, bibliographic information and all other significant items in recently published issues from over 1,000 leading journals in clinical medicine.

BIOSIS Previews BIOSIS Previews is an English-language, bibliographic database service, with abstracts and citation indexing. It is part of Clarivate Analytics Web of Science suite. BIOSIS Previews indexes data from 1926 to the present.

Journal Citation Reports/Science Edition Journal Citation Reports/Science Edition aims to evaluate a journal’s value from multiple perspectives including the journal impact factor, descriptive data about a journal’s open access content as well as contributing authors, and provide readers a transparent and publisher-neutral data & statistics information about the journal.

Submission Turnaround Time

Conferences

Top