Interleukin-8: A potent promoter of human lymphatic endothelial cell growth in gastric cancer

Shi,Jun; Li,Yong-Jin; Yan,Bing; Wei,Pin-Kang

doi:10.3892/or.2015.3916

Interleukin-8: A potent promoter of human lymphatic endothelial cell growth in gastric cancer

Authors:
- Jun Shi
- Yong-Jin Li
- Bing Yan
- Pin-Kang Wei
View Affiliations

Affiliations: Department of Traditional Chinese Medicine, Shanghai Changzheng Hospital, The Second Military Medical University, Shanghai, P.R. China
Published online on: April 17, 2015 https://doi.org/10.3892/or.2015.3916
Pages: 2703-2710
Copyright: © Shi et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Lymphatic metastasis is a major progression route of gastric cancer. Interleukin-8 (IL-8), as an inflammatory cytokine, is induced by Helicobacter pylori infection and is strongly associated with gastric cancer development and metastasis. The blood and lymphatic systems are similar in their function and gene expression profiles. It has been proposed that IL-8 activates angiogenesis. However, the direct role of IL-8 in lymphangiogenesis in gastric cancer remains unclear. We investigated the effect of IL-8 on the growth of human lymphatic endothelial cells (LECs). In addition, protein and mRNA expression of selected lymphangiogenesis markers was assessed in these cells. LECs were co-cultured with gastric cancer SGC7901 cells and exposed to various concentrations of IL-8 (0, 0.2, 0.5, 0.8 and 1.0 ng/ml). The Cell Counting Kit-8 was used to evaluate LEC proliferation (cultured for 1-6 days). Then, protein (immunofluorescence and western blotting) and mRNA [quantitative transcription-polymerase chain reaction (qPCR)] levels were measured in samples obtained from the 24-h cultured cells, for lymphatic vessel endothelial hyaluronic acid receptor-1 (LYVE-1), vascular endothelial growth factor (VEGF)-C, VEGF-D and vascular endothelial growth factor receptor-3 (VEGFR-3). The data presented herein demonstrated that IL-8 promotes the proliferation of LECs and enhances the protein and mRNA expression of LYVE-1. Notably, IL-8 inhibited VEGF-C, VEGF-D and VEGFR-3 protein expression as well as VEGF-D and VEGFR-3 mRNA expression. These findings suggest that IL-8 may be a potent inducer of LECs, although this effect does not appear to involve the VEGF-C/VEGF-D and VEGFR-3 signaling pathway.

View Figures

View References

1	Ren Z, Pang G, Clancy R, Li LC, Lee CS, Batey R, Borody T and Dunkley M: Shift of the gastric T-cell response in gastric carcinoma. J Gastroenterol Hepatol. 16:142–148. 2001. View Article : Google Scholar : PubMed/NCBI
2	Kitadai Y, Haruma K, Mukaida N, Ohmoto Y, Matsutani N, Yasui W, Yamamoto S, Sumii K, Kajiyama G, Fidler IJ, et al: Regulation of disease-progression genes in human gastric carcinoma cells by interleukin 8. Clin Cancer Res. 6:2735–2740. 2000.PubMed/NCBI
3	Kuai WX, Wang Q, Yang XZ, Zhao Y, Yu R and Tang XJ: Interleukin-8 associates with adhesion, migration, invasion and chemosensitivity of human gastric cancer cells. World J Gastroenterol. 18:979–985. 2012. View Article : Google Scholar : PubMed/NCBI
4	Waugh DJ and Wilson C: The interleukin-8 pathway in cancer. Clin Cancer Res. 14:6735–6741. 2008. View Article : Google Scholar : PubMed/NCBI
5	Zhao ZS, Wang YY, Chu YQ, Ye ZY and Tao HQ: SPARC is associated with gastric cancer progression and poor survival of patients. Clin Cancer Res. 16:260–268. 2010. View Article : Google Scholar
6	Petrova TV, Mäkinen T, Mäkelä TP, Saarela J, Virtanen I, Ferrell RE, Finegold DN, Kerjaschki D, Ylä-Herttuala S and Alitalo K: Lymphatic endothelial reprogramming of vascular endothelial cells by the Prox-1 homeobox transcription factor. EMBO J. 21:4593–4599. 2002. View Article : Google Scholar : PubMed/NCBI
7	Hirakawa S, Hong YK, Harvey N, Schacht V, Matsuda K, Libermann T and Detmar M: Identification of vascular lineage-specific genes by transcriptional profiling of isolated blood vascular and lymphatic endothelial cells. Am J Pathol. 162:575–586. 2003. View Article : Google Scholar : PubMed/NCBI
8	Hong YK, Harvey N, Noh YH, Schacht V, Hirakawa S, Detmar M and Oliver G: Prox1 is a master control gene in the program specifying lymphatic endothelial cell fate. Dev Dyn. 225:351–357. 2002. View Article : Google Scholar : PubMed/NCBI
9	Koch AE, Polverini PJ, Kunkel SL, Harlow LA, DiPietro LA, Elner VM, Elner SG and Strieter RM: Interleukin-8 as a macrophage-derived mediator of angiogenesis. Science. 258:1798–1801. 1992. View Article : Google Scholar : PubMed/NCBI
10	Strieter RM, Kunkel SL, Elner VM, Martonyi CL, Koch AE, Polverini PJ and Elner SG: Interleukin-8. A corneal factor that induces neovascularization. Am J Pathol. 141:1279–1284. 1992.PubMed/NCBI
11	Kim H, Kataru RP and Koh GY: Regulation and implications of inflammatory lymphangiogenesis. Trends Immunol. 33:350–356. 2012. View Article : Google Scholar : PubMed/NCBI
12	Bernaudin JF, Kambouchner M and Lacave R: Lymphatic vascular system, development and lymph formation. Review Rev Pneumol Clin. 69:93–101. 2013.In French. View Article : Google Scholar
13	Yu H, Zhang S, Zhang R and Zhang L: The role of VEGF-C/D and Flt-4 in the lymphatic metastasis of early-stage invasive cervical carcinoma. J Exp Clin Cancer Res. 28:982009. View Article : Google Scholar : PubMed/NCBI
14	Harada A, Sekido N, Akahoshi T, Wada T, Mukaida N and Matsushima K: Essential involvement of interleukin-8 (IL-8) in acute inflammation. J Leukoc Biol. 56:559–564. 1994.PubMed/NCBI
15	Raman D, Baugher PJ, Thu YM and Richmond A: Role of chemokines in tumor growth. Cancer Lett. 256:137–165. 2007. View Article : Google Scholar : PubMed/NCBI
16	Xie K: Interleukin-8 and human cancer biology. Cytokine Growth Factor Rev. 12:375–391. 2001. View Article : Google Scholar : PubMed/NCBI
17	Uemura N, Okamoto S, Yamamoto S, Matsumura N, Yamaguchi S, Yamakido M, Taniyama K, Sasaki N and Schlemper RJ: Helicobacter pylori infection and the development of gastric cancer. N Engl J Med. 345:784–789. 2001. View Article : Google Scholar : PubMed/NCBI
18	Correa P and Houghton J: Carcinogenesis of Helicobacter pylori. Gastroenterology. 133:659–672. 2007. View Article : Google Scholar : PubMed/NCBI
19	Crabtree JE, Farmery SM, Lindley IJ, Figura N, Peichl P and Tompkins DS: CagA/cytotoxic strains of Helicobacter pylori and interleukin-8 in gastric epithelial cell lines. J Clin Pathol. 47:945–950. 1994. View Article : Google Scholar : PubMed/NCBI
20	Sharma SA, Tummuru MK, Miller GG and Blaser MJ: Interleukin-8 response of gastric epithelial cell lines to Helicobacter pylori stimulation in vitro. Infect Immun. 63:1681–1687. 1995.PubMed/NCBI
21	Campbell LM, Maxwell PJ and Waugh DJ: Rationale and means to target pro-inflammatory interleukin-8 (CXCL8) signaling in cancer. Pharmaceuticals. 6:929–959. 2013. View Article : Google Scholar : PubMed/NCBI
22	Ju D, Sun D, Xiu L, Meng X, Zhang C and Wei P: Interleukin-8 is associated with adhesion, migration and invasion in human gastric cancer SCG-7901 cells. Med Oncol. 29:91–99. 2012. View Article : Google Scholar
23	Scavelli C, Weber E, Aglianò M, Cirulli T, Nico B, Vacca A and Ribatti D: Lymphatics at the crossroads of angiogenesis and lymphangiogenesis. J Anat. 204:433–449. 2004. View Article : Google Scholar : PubMed/NCBI
24	Achen MG and Stacker SA: Tumor lymphangiogenesis and metastatic spread - new players begin to emerge. Int J Cancer. 119:1755–1760. 2006. View Article : Google Scholar : PubMed/NCBI
25	Pepper MS, Tille JC, Nisato R and Skobe M: Lymphangiogenesis and tumor metastasis. Cell Tissue Res. 314:167–177. 2003. View Article : Google Scholar : PubMed/NCBI
26	Nakamura Y, Yasuoka H, Tsujimoto M, Kurozumi K, Nakahara M, Nakao K and Kakudo K: Importance of lymph vessels in gastric cancer: A prognostic indicator in general and a predictor for lymph node metastasis in early stage cancer. J Clin Pathol. 59:77–82. 2006. View Article : Google Scholar : PubMed/NCBI
27	Alitalo K, Tammela T and Petrova TV: Lymphangiogenesis in development and human disease. Nature. 438:946–953. 2005. View Article : Google Scholar : PubMed/NCBI
28	Achen MG, McColl BK and Stacker SA: Focus on lymphangio-genesis in tumor metastasis. Cancer Cell. 7:121–127. 2005. View Article : Google Scholar : PubMed/NCBI
29	Shimizu K, Kubo H, Yamaguchi K, Kawashima K, Ueda Y, Matsuo K, Awane M, Shimahara Y, Takabayashi A, Yamaoka Y, et al: Suppression of VEGFR-3 signaling inhibits lymph node metastasis in gastric cancer. Cancer Sci. 95:328–333. 2004. View Article : Google Scholar : PubMed/NCBI
30	Al-Rawi MA and Jiang WG: Lymphangiogenesis and cancer metastasis. Front Biosci. 16:723–739. 2011. View Article : Google Scholar
31	Medina-Franco H, Cabrera-Mendoza F, Almaguer-Rosales S, Guillén F, Suárez-Bobadilla YL and Sánchez-Ramón A: Lymph node ratio as a predictor of survival in gastric carcinoma. Am Surg. 79:284–289. 2013.PubMed/NCBI
32	Tawada M, Hayashi S, Osada S, Nakashima S and Yoshida K: Human gastric cancer organizes neighboring lymphatic vessels via recruitment of bone marrow-derived lymphatic endothelial progenitor cells. J Gastroenterol. 47:1057–1060. 2012. View Article : Google Scholar : PubMed/NCBI
33	Choi I, Lee YS, Chung HK, Choi D, Ecoiffier T, Lee HN, Kim KE, Lee S, Park EK, Maeng YS, et al: Interleukin-8 reduces post-surgical lymphedema formation by promoting lymphatic vessel regeneration. Angiogenesis. 16:29–44. 2013. View Article : Google Scholar
34	Mu H, Calderone TL, Davies MA, Prieto VG, Wang H, Mills GB, Bar-Eli M and Gershenwald JE: Lysophosphatidic acid induces lymphangiogenesis and IL-8 production in vitro in human lymphatic endothelial cells. Am J Pathol. 180:2170–2181. 2012. View Article : Google Scholar : PubMed/NCBI
35	Sakai Y, Goodison S, Kusmartsev S, Fletcher B, Eruslanov E, Cao W, Porvasnik S, Namiki K, Anai S and Rosser CJ: Bcl-2 mediated modulation of vascularization in prostate cancer xeno-grafts. Prostate. 69:459–470. 2009. View Article : Google Scholar
36	Al-Rawi MA, Mansel RE and Jiang WG: Molecular and cellular mechanisms of lymphangiogenesis. Eur J Surg Oncol. 31:117–121. 2005. View Article : Google Scholar : PubMed/NCBI
37	Platonova N, Miquel G, Regenfuss B, Taouji S, Cursiefen C, Chevet E and Bikfalvi A: Evidence for the interaction of fibroblast growth factor-2 with the lymphatic endothelial cell marker LYVE-1. Blood. 121:1229–1237. 2013. View Article : Google Scholar
38	Leung DW, Cachianes G, Kuang WJ, Goeddel DV and Ferrara N: Vascular endothelial growth factor is a secreted angiogenic mitogen. Science. 246:1306–1309. 1989. View Article : Google Scholar : PubMed/NCBI
39	Schoppmann SF, Birner P, Stöckl J, Kalt R, Ullrich R, Caucig C, Kriehuber E, Nagy K, Alitalo K and Kerjaschki D: Tumor-associated macrophages express lymphatic endothelial growth factors and are related to peritumoral lymphangiogenesis. Am J Pathol. 161:947–956. 2002. View Article : Google Scholar : PubMed/NCBI
40	Ming J, Zhang Q, Qiu X and Wang E: Interleukin 7/interleukin 7 receptor induce c-Fos/c-Jun-dependent vascular endothelial growth factor-D up-regulation: A mechanism of lymphangiogenesis in lung cancer. Eur J Cancer. 45:866–873. 2009. View Article : Google Scholar : PubMed/NCBI
41	Matsumoto M, Roufail S, Inder R, Caesar C, Karnezis T, Shayan R, Farnsworth RH, Sato T, Achen MG, Mann GB, et al: Signaling for lymphangiogenesis via VEGFR-3 is required for the early events of metastasis. Clin Exp Metastasis. 30:819–832. 2013. View Article : Google Scholar : PubMed/NCBI
42	Ji RC: Lymph node lymphangiogenesis: A new concept for modulating tumor metastasis and inflammatory process. Histol Histopathol. 24:377–384. 2009.PubMed/NCBI
43	Matsumura S, Oue N, Mitani Y, Kitadai Y and Yasui W: DNA demethylation of vascular endothelial growth factor-C is associated with gene expression and its possible involvement of lymphangio-genesis in gastric cancer. Int J Cancer. 120:1689–1695. 2007. View Article : Google Scholar : PubMed/NCBI
44	Kodama M, Kitadai Y, Tanaka M, Kuwai T, Tanaka S, Oue N, Yasui W and Chayama K: Vascular endothelial growth factor C stimulates progression of human gastric cancer via both autocrine and paracrine mechanisms. Clin Cancer Res. 14:7205–7214. 2008. View Article : Google Scholar : PubMed/NCBI
45	Yuanming L, Feng G, Lei T and Ying W: Quantitative analysis of lymphangiogenic markers in human gastroenteric tumor. Arch Med Res. 38:106–112. 2007. View Article : Google Scholar
46	Zhu P, Zhang J, Chen Q, Wang J and Wang Y: Expression of vascular endothelial growth factor-C in gastric carcinoma and the effect of its antisense gene transfection on the proliferation of human gastric cancer cell line SGC-7901. Am J Surg. 204:78–83. 2012. View Article : Google Scholar : PubMed/NCBI
47	Yashiro M, Shinto O, Nakamura K, Tendo M, Matsuoka T, Matsuzaki T, Kaizaki R, Ohira M, Miwa A and Hirakawa K: Effects of VEGFR-3 phosphorylation inhibitor on lymph node metastasis in an orthotopic diffuse-type gastric carcinoma model. Br J Cancer. 101:1100–1106. 2009. View Article : Google Scholar : PubMed/NCBI
48	Yonemura Y, Endo Y, Tabata K, Kawamura T, Yun HY, Bandou E, Sasaki T and Miura M: Role of VEGF-C and VEGF-D in lymphangiogenesis in gastric cancer. Int J Clin Oncol. 10:318–327. 2005. View Article : Google Scholar : PubMed/NCBI
49	Kitadai Y, Kodama M, Cho S, Kuroda T, Ochiumi T, Kimura S, Tanaka S, Matsumura S, Yasui W and Chayama K: Quantitative analysis of lymphangiogenic markers for predicting metastasis of human gastric carcinoma to lymph nodes. Int J Cancer. 115:388–392. 2005. View Article : Google Scholar : PubMed/NCBI
50	Krzystek-Korpacka M, Matusiewicz M, Diakowska D, Grabowski K, Blachut K, Konieczny D, Kustrzeba-Wojcicka I, Terlecki G and Banas T: Elevation of circulating interleukin-8 is related to lymph node and distant metastases in esophageal squamous cell carcinomas - implication for clinical evaluation of cancer patient. Cytokine. 41:232–239. 2008. View Article : Google Scholar : PubMed/NCBI
51	Sharma SA, Tummuru MK, Blaser MJ and Kerr LD: Activation of IL-8 gene expression by Helicobacter pylori is regulated by transcription factor nuclear factor-kappa B in gastric epithelial cells. J Immunol. 160:2401–2407. 1998.PubMed/NCBI
52	Watari K, Nakao S, Fotovati A, Basaki Y, Hosoi F, Bereczky B, Higuchi R, Miyamoto T, Kuwano M and Ono M: Role of macrophages in inflammatory lymphangiogenesis: Enhanced production of vascular endothelial growth factor C and D through NF-kappaB activation. Biochem Biophys Res Commun. 377:826–831. 2008. View Article : Google Scholar : PubMed/NCBI