Abstract
Interleukin-8 is known as an important chemokine involved in tumor angiogenesis and progression. Overexpression of interleukin-8 has been detected in a variety of human tumors, including gastric cancer, and is negatively correlated with prognosis. The aim of our study is to determine the effects of interleukin-8 on proliferation, adhesion, migration and invasion abilities and correlated molecular mechanisms in gastric cancer. We made recombinant interleukin-8 ranged from 0 ng/ml to 100 ng/ml interferes in human gastric cancer SCG-7901 cells in vitro. The results shown that interleukin-8 did not change cell proliferation, but promoted cell adhesion to endothelial cell and extracellular matrix components (collagen, laminin and fibronectin) as detected by Cell Counting Kit-8. And it induced migration and invasion ability based on scratch and transwell-chamber assays. Also, interleukin-8 regulated the protein and mRNA expression of matrix metalloproteinase-9, intercellular adhesion molecule-1 and E-cad and there was obviously a dose-dependent relationship, but the protein or mRNA expression of matrix metalloproteinase-2 was not obviously changed under the tested conditions. Our findings indicate that interleukin-8 is associated with adhesion, migration and invasion in gastric cancer and the regulation of matrix metalloproteinase-9, intercellular adhesion molecule-1 and E-cad expression is one of the potential molecule mechanisms. The studies imply interleukin-8 may be an alternative treatment strategy against gastric cancer.
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References
Krejs GJ. Gastric cancer: epidemiology and risk factors. Dig Dis. 2010;28(4–5):600–3. (Epub 18 Nov 2010).
Kamangar F, Dores GM, Anderson WF. Patterns of cancer incidence, mortality, and prevalence across five continents: defining priorities to reduce cancer disparities in different geographic regions of the world. J Clin Oncol. 2006;24(14):2137–50.
Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108.
Gabellini C, Trisciuoglio D, Desideri M, Candiloro A, Ragazzoni Y, Orlandi A, Zupi G, Del Bufalo D. Functional activity of CXCL8 receptors, CXCR1 and CXCR2, on human malignant melanoma progression. Eur J Cancer. 2009;45(14):2618–27. (Epub 13 Aug 2009).
Kamohara H, Takahashi M, Ishiko T, Ogawa M, Baba H. Induction of interleukin-8 (CXCL-8) by tumor necrosis factor-alpha and leukemia inhibitory factor in pancreatic carcinoma cells: impact of CXCL-8 as an autocrine growth factor. Int J Oncol. 2007;31(3):627–32.
Itoh Y, Joh T, Tanida S, Sasaki M, Kataoka H, Itoh K, Oshima T, Ogasawara N, Togawa S, Wada T, Kubota H, Mori Y, Ohara H, Nomura T, Higashiyama S, Itoh M. IL-8 promotes cell proliferation and migration through metalloproteinase-cleavage proHB-EGF in human colon carcinoma cells. Cytokine. 2005;29(6):275–82.
Merritt WM, Lin YG, Spannuth WA, Fletcher MS, Kamat AA, Han LY, Landen CN, Jennings N, De Geest K, Langley RR, Villares G, Sanguino A, Lutgendorf SK, Lopez-Berestein G, Bar-Eli MM, Sood AK. Effect of interleukin-8 gene silencing with liposome-encapsulated small interfering RNA on ovarian cancer cell growth. J Natl Cancer Inst. 2008;100(5):359–72. (Epub 2008 Feb 26).
Matsuo Y, Ochi N, Sawai H, Yasuda A, Takahashi H, Funahashi H, Takeyama H, Tong Z, Guha S. CXCL8/IL-8 and CXCL12/SDF-1alpha co-operatively promote invasiveness and angiogenesis in pancreatic cancer. Int J Cancer. 2009;124(4):853–61.
Kitadai Y, Takahashi Y, Haruma K, Naka K, Sumii K, Yokozaki H, Yasui W, Mukaida N, Ohmoto Y, Kajiyama G, Fidler IJ, Tahara E. Transfection of interleukin-8 increases angiogenesis and tumorigenesis of human gastric carcinoma cells in nude mice. Br J Cancer. 1999;81(4):647–53.
Ning Y, Manegold PC, Hong YK, Zhang W, Pohl A, Lurje G, Winder T, Yang D, Labonte MJ, Wilson PM, Ladner RD, Lenz HJ. Interleukin-8 is associated with proliferation, migration, angiogenesis and chemosensitivity in vitro and in vivo in colon cancer cell line models. Int J Cancer. 20 July 2010. (Epub ahead of print).
Singh RK, Lokeshwar BL. Depletion of intrinsic expression of Interleukin-8 in prostate cancer cells causes cell cycle arrest, spontaneous apoptosis and increases the efficacy of chemotherapeutic drugs. Mol Cancer. 2009;8:57.
Song B, Zhang D, Wang S, Zheng H, Wang X. Association of interleukin-8 with cachexia from patients with low-third gastric cancer. Comp Funct Genomics. 23 Nov 2009 (Epub ahead of print).
Millar HJ, Nemeth JA, McCabe FL, Pikounis B, Wickstrom E. Circulating human interleukin-8 as an indicator of cancer progression in a nude rat orthotopic human non-small cell lung carcinoma model. Cancer Epidemiol Biomarkers Prev. 2008;17(8):2180–7.
Chen JJ, Yao PL, Yuan A, Hong TM, Shun CT, Kuo ML, Lee YC, Yang PC. Up-regulation of tumor interleukin-8 expression by infiltrating macrophages: its correlation with tumor angiogenesis and patient survival in non-small cell lung cancer. Clin Cancer Res. 2003;9(2):729–37.
Kido S, Kitadai Y, Hattori N, Haruma K, Kido T, Ohta M, Tanaka S, Yoshihara M, Sumii K, Ohmoto Y, Chayama K. Interleukin 8 and vascular endothelial growth factor—prognostic factors in human gastric carcinomas? Eur J Cancer. 2001;37(12):1482–7.
Konno H, Ohta M, Baba M, Suzuki S, Nakamura S. The role of circulating IL-8 and VEGF protein in the progression of gastric cancer. Cancer Sci. 2003;94(8):735–40.
Wang J, Pan HF, Hu YT, Zhu Y, He Q. Polymorphism of IL-8 in 251 allele and gastric cancer susceptibility: a meta-analysis. Dig Dis Sci. 2010;55(7):1818–23. (Epub 24 Sep 2009).
Kitadai Y, Haruma K, Mukaida N, Ohmoto Y, Matsutani N, Yasui W, Yamamoto S, Sumii K, Kajiyama G, Fidler IJ, Tahara E. Regulation of disease-progression genes in human gastric carcinoma cells by interleukin 8. Clin Cancer Res. 2000;6(7):2735–40.
Schadendorf M, Algermissen W, Sticherling C. IL-8 produced by human malignant melanoma cells in vitro is an essential autocrine growth factor. J Immunol. 1994;153(7):3360.
Doll D, Keller L, Maak M, Boulesteix AL, Siewert JR, Holzmann B, Janssen KP. Differential expression of the chemokines GRO-2, GRO-3, and interleukin-8 in colon cancer and their impact on metastatic disease and survival. Int J Colorectal Dis. 2010;25(5):573–81. (Epub 17 Feb 2010).
Li M, Zhang Y, Feurino LW, Wang H, Fisher WE, Brunicardi FC, Chen C, Yao Q. Interleukin-8 increases vascular endothelial growth factor and neuropilin expression and stimulates ERK activation in human pancreatic cancer. Cancer Sci. 2008;99(4):733–7. (Epub 27 Feb 2008).
Kubo F, Ueno S, Hiwatashi K, Sakoda M, Kawaida K, Nuruki K, Aikou T. Interleukin 8 in human hepatocellular carcinoma correlates with cancer cell invasion of vessels but not with tumor angiogenesis. Ann Surg Oncol. 2005;12(10):800–7. (Epub 9 Aug 2005).
Baggiolini M, Clark-Lewis I. Interleukin-8, a chemotactic and inflammatory cytokine. FEBS Lett. 1992;307(1):97–101.
Luppi F, Longo AM, de Boer WI, Rabe KF, Hiemstra PS. Interleukin-8 stimulates cell proliferation in non-small cell lung cancer through epidermal growth factor receptor transactivation. Lung Cancer. 2007;56(1):25–33. Epub 2006 Dec 15.
Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100(1):57–70.
Haier J, Nasralla M, Nicolson GL. Cell surface molecules and their prognostic values in assessing colorectal carcinomas. Ann Surg. 2000;231:11–24.
Cavallaro U, Christofori G. Multitasking in tumor progression: signaling functions of cell adhesion molecules. Ann N Y Acad Sci. 2004;1014:58–66.
Lazăr D, Tăban S, Ardeleanu C, Dema A, Sporea I, Cornianu M, Lazăr E, Vernic C. The immunohistochemical expression of E-cadherin in gastric cancer; correlations with clinicopathological factors and patients’ survival. Rom J Morphol Embryol. 2008;49(4):459–67.
Aoki R, Yasuda M, Torisu R, Nakamoto J, Yamamoto Y, Ito S. Relationship between lymph node metastasis and E-cadherin expression in submucosal invasive gastric carcinomas with gastric-phenotype. J Med Invest. 2007;54(1–2):159–67.
Humar B, Blair V, Charlton A, More H, Martin I, Guilford P. E-cadherin deficiency initiates gastric signet-ring cell carcinoma in mice and man. Cancer Res. 2009;69(5):2050–6. (Epub 17 Feb 2009).
Tang B, Peng ZH, Yu PW, Yu G, Qian F. Expression and significance of Cx43 and E-cadherin in gastric cancer and metastatic lymph nodes. Med Oncol. 6 Apr 2010. (Epub ahead of print).
Yashiro M, Sunami T, Hirakawa K. CD54 expression is predictive for lymphatic spread in human gastric carcinoma. Dig Dis Sci. 2005;50(12):2224–30.
Shin HS, Jung CH, Park HD, Lee SS. The relationship between the serum intercellular adhesion molecule-1 level and the prognosis of the disease in lung cancer. Korean J Intern Med. 2004;19(1):48–52.
Gallicchio M, Rosa AC, Dianzani C, Brucato L, Benetti E, Collino M, Fantozzi R. Celecoxib decreases expression of the adhesion molecules ICAM-1 and VCAM-1 in a colon cancer cell line (HT29). Br J Pharmacol. 2008;153(5):870–8. (Epub 17 Dec 2007).
Hayes SH, Seigel GM. Immunoreactivity of ICAM-1 in human tumors, metastases and normal tissues. Int J Clin Exp Pathol. 2009;2(6):553–60.
Nagase H, Woessner JF Jr. Matrix metalloproteinases. J Biol Chem. 1999;274(31):21491–4.
Mandal M, Mandal A, Das S, Chakraborti T, Sajal C. Clinical implications of matrix metalloproteinases. Mol Cell Biochem. 2003;252(1–2):305–29.
van der Jagt MF, Sweep FC, Waas ET, Hendriks T, Ruers TJ, Merry AH, Wobbes T, Span PN. Correlation of reversion-inducing cysteine-rich protein with kazal motifs (RECK) and extracellular matrix metalloproteinase inducer (EMMPRIN), with MMP-2, MMP-9, and survival in colorectal cancer. Cancer Lett. 2006;237(2):289–97. (Epub 19 July 2005).
Peng CW, Liu XL, Liu X, Li Y. Co-evolution of cancer microenvironment reveals distinctive patterns of gastric cancer invasion: laboratory evidence and clinical significance. J Transl Med. 2010;8:101.
Daniele A, Zito AF, Giannelli G, Divella R, Asselti M, Mazzocca A, Paradiso A, Quaranta M. Expression of metalloproteinases MMP-2 and MMP-9 in sentinel lymph node and serum of patients with metastatic and non-metastatic breast cancer. Anticancer Res. 2010;30(9):3521–7.
Lu MK, Shih YW, Chang Chien TT, Fang LH, Huang HC, Chen PS. α-Solanine inhibits human melanoma cell migration and invasion by reducing matrix metalloproteinase-2/9 activities. Biol Pharm Bull. 2010;33(10):1685–91.
Watanabe H, Iwase M, Ohashi M, Nagumo M. Role of interleukin-8 secreted from human oral squamous cell carcinoma cell lines. Oral Oncol. 2002;38(7):670–9.
Ning Y, Manegold PC, Hong YK, Zhang W, Pohl A, Lurje G, Winder T, Yang D, Labonte MJ, Wilson PM, Ladner RD, Lenz HJ. Interleukin-8 is associated with proliferation, migration, angiogenesis and chemosensitivity in vitro and in vivo in colon cancer cell line models. Int J Cancer. 20 July 2010. (Epub ahead of print).
Inoue K, Slaton JW, Kim SJ, Perrotte P, Eve BY, Bar-Eli M, Radinsky R, Dinney CP. Interleukin 8 expression regulates tumorigenicity and metastasis in human bladder cancer. Cancer Res. 2000;60(8):2290–9.
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This work was supported by grant No. 90709044 from the National Natural Science Foundation of China.
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Ju, D., Sun, D., Xiu, L. et al. Interleukin-8 is associated with adhesion, migration and invasion in human gastric cancer SCG-7901 cells. Med Oncol 29, 91–99 (2012). https://doi.org/10.1007/s12032-010-9780-0
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DOI: https://doi.org/10.1007/s12032-010-9780-0