Interleukin (IL)-32 is proinflammatory cytokine, which has been shown to play an important role in cancer growth and metastasis. Here, we investigated whether the proinflammatory cytokine IL-32 may be involved in colonic carcinogenesis through upregulation of matrix metalloproteinase (MMP)-2. We are obtaining consent from all patients, 136 patients (88 males and 48 females; median age, 57 years; range 38–8 years) diagnosed patholgically with colonic cancer from 2014 to 2017 were participated in the study. Tumor tissue and adjacent noncancerous mucosa were harvested immediately following colonic resection. Quantitative reverse transcription PCR (qRT-PCR) was performed using SYBR green. Formalin-fixed and paraffin-embedded tissues were examined with immunohistochemistry (IHC) using primary antibody. Our results clearly suggest that IL-32 is an important mediator for colonic cancer metastasis and independent prognostic predictor of colonic cancer. Moreover, IL-32-facilitated cell migration and invasion in vitro was mediated through upregulation of matrix metalloproteinase (MMP)-2 expression. These data demonstrate that IL-32 plays a critical role in invasion and metastasis of colon cancer.
Keywords: IL-32; Colonic cancer; PCR; Matrix metalloproteinase (MMP)-2
Copyright © 2018 by The American Society for BioMedicine and BM-Publisher, Inc.
1. Surveillance, Epidemiology, and End Results (SEER) Program. Stat Fact Sheets: Colon and Rectum Cancer. [(accessed on 25 October 2013)]. Available online: http://seer.Cancer.Gov/statfacts/html/colorect.Html/
2. Howlader N, Noone A, Krapcho M, et al. SEER Cancer Statistics Review, 1975–2008. National Cancer Institute; Bethesda, MD, USA: 2011.
3. Hua H, Li M, Luo T, Yin Y, Jiang Y. Matrix metalloproteinases in tumorigenesis: An evolving paradigm. Cell. Mol. Life Sci 2011;68:3853–3868.
4. Van der Jagt MF, Wobbes T, Strobbe LJ, Sweep FC, Span PN. Metalloproteinases and their regulators in colorectal cancer. J. Surg. Oncol 2010;101:259–269.
5. Yousif NG, Zhai Y, Slimani H, Ao L, Fullerton D, Meng X. TLR3-mediated inflammatory response after global myocardial i/r via activation of TLR4-mediated NF-kappa β and TRIF/IRF signaling pathways. SHOCK 2014;41: 34-34.
6. Hu J, van den Steen PE, Sang Q, Opdenakker G. Matrix metalloproteinase inhibitors as therapy for inflammatory and vascular diseases. Nat. Rev. Drug Discov. 2007;6:480–498.
7. Doyle JL, Haas TL. Differential role of b-catenin in VEGF and histamineinduced MMP-2 production in microvascular endothelial cells. J Cell Biochem 2009;107:272–83.
8. Clements WM, Wang J, Sarnaik A, Kim OJ, MacDonald J, FenoglioPreiser C, et al. b-Catenin mutation is a frequent cause of Wnt pathway activation in gastric cancer. Cancer Res 2002;62:3503–6.
9. Yousif NG. Fibronectin promotes migration and invasion of ovarian cancer cells through up‐regulation of FAK–PI 3 K/A kt pathway. Cell biology international 2014;38: 85-91.
10. Cho JY, Lim JY, Cheong JH, Park YY, Yoon SL, Kim SM, et al. Gene expression signature-based prognostic risk score in gastric cancer. Clin Cancer Res 2011;17:1850–7.
11. Catalano V, Labianca R, Beretta GD, Gatta G, de Braud F, Van Cutsem E. Gastric cancer. Crit Rev Oncol Hematol 2009;71:127–64.
12. Naylor TL, Greshock J, Wang Y, Colligon T, Yu QC, Clemmer V, et al. High resolution genomic analysis of sporadic breast cancer using array-based comparative genomic hybridization. Breast Cancer Res 2005;7:R1186–98.
13. Shoda H, Fujio K, Yamamoto K. Rheumatoid arthritis and interleukin32. Cell Mol Life Sci 2007;64:2671–9.
14. Yousif NG, Al-Amran FG, Hadi N, Lee J, Adrienne J. Expression of IL-32 modulates NF-κB and p38 MAP kinase pathways in human esophageal cancer. Cytokine 2013;61: 223-227.
15. Coussens LM, Fingleton B, Matrisian LM. Matrix metalloproteinase inhibitors and cancer: Trials and tribulations. Science 2002;295:2387–2392.
16. Ogata Y, Matono K, Nakajima M, et al. Efficacy of the mmp inhibitor mmi270 against lung metastasis following removal of orthotopically transplanted human colon cancer in rat. Int. J. Cancer. 2006;118:215–221.
17. Roy R, Yang J, Moses MA. Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer. J. Clin. Oncol 2009;27:5287–5297.
18. Hasegawa S, Koshikawa N, Momiyama N, et al. Matrilysin-specific antisense oligonucleotide inhibits liver metastasis of human colon cancer cells in a nude mouse model. Int. J. Cancer 1998;76:812–816.
19. Wu J, Wu G, Lv L, et al. Microrna-34a inhibits migration and invasion of colon cancer cells via targeting to fra-1. Carcinogenesis 2012;33:519–528.
20. Novick D, Rubinstein M, Azam T, Rabinkov A, Dinarello CA, Kim SH. Proteinase 3 is an IL-32 binding protein. Proc Natl Acad Sci U S A 2006;103:3316–21.
21. Netea MG, Azam T, Ferwerda G, et al. IL-32 synergizes with nucleotide oligomerization domain (NOD) 1 and NOD2 ligands for IL-1b and IL-6 production through a caspase 1- dependent mechanism. Proc Natl Acad Sci U S A 2005;102:16309–14. 18.
22. Japanese Gastric Cancer A. Japanese classification of gastric carcinoma—2nd English edition. Gastric Cancer 1998;1:10–24. https://doi.org/10.1007/s101200050051
23. Yousif NG, Sadiq AM, Yousif MG, Al-Mudhafar RH. Notch1 ligand signaling pathway activated in cervical cancer: poor prognosis with high-level JAG1/Notch1. Archives of gynecology and obstetrics 2015;4: 899-904.
24. Shih CH, Chen SL, Yen CC, et al. Thyroid hormone receptor-dependent transcriptional regulation of fibrinogen and coagulation proteins. Endocrinology 2004;145:2804–14.
25. Alhasani S, Yousif NG. Critical role of IL-23 signaling in prostatic cancer. American Journal of BioMedicine 2013;1(1): 4-6.
26. Wang CL, Wang CI, Liao PC, et al. Discovery of retinoblastoma-associated binding protein 46 as a novel prognostic marker for distant metastasis in nonsmall cell lung cancer by combined analysis of cancer cell secretome and pleural effusion proteome. J Proteome Res 2009;8:4428–40.
27. Lee JH, Choi JW, Kim YS. Plasma or serum timp-1 is a predictor of survival outcomes in colorectal cancer: A meta-analysis. J. Gastrointest. Liver Dis 2011;20:287–291.
28. Holten-Andersen MN, Christensen IJ, Nielsen HJ, et al. Total levels of tissue inhibitor of metalloproteinases 1 in plasma yield high diagnostic sensitivity and specificity in patients with colon cancer. Clin. Cancer Res 2002;8:156–164.
29. Wang DG, Yousif NG, Sadiq AM, et al. Critical role of SEMA5A expression in invasion and metastasis of ovarian cancer cell. American Journal of BioMedicine 2014;2(3): 4-6.
30. Lu KV, Jong KA, Rajasekaran AK, Cloughesy TF, Mischel PS. Upregulation of tissue inhibitor of metalloproteinases (timp)-2 promotes matrix metalloproteinase (mmp)-2 activation and cell invasion in a human glioblastoma cell line. Lab. Investig 2004;84:8–20.
31. Park KS, Kim SJ, Kim KH, Kim JC. Clinical characteristics of timp2, mmp2, and mmp9 gene polymorphisms in colorectal cancer. J. Gastroenterol. Hepatol 2011;26:391–397.
32. Zhang M, Liu Y, Feng H, et al. Cd133 affects the invasive ability of hct116 cells by regulating timp-2. Am. J. Pathol 2013;182:565–576.
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American Journal of BioMedicine Volume 6, Issue 8, pages 661-684
Received July 28, 2018; accepted October 16, 2018; published October 24, 2018
How to cite this article
Tsai C, Kim H, Adriennea J. Critical role of IL-32 invasion and metastasis of colonic cancer through upregulation of matrix metalloproteinase (MMP)-2. American Journal of BioMedicine 2018;6(10):661-684.
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