Skip to main content
Erschienen in: Cancer Immunology, Immunotherapy 2/2015

01.02.2015 | Original Article

Dynamics of the IL-33/ST2 network in the progression of human colorectal adenoma to sporadic colorectal cancer

verfasst von: Guanglin Cui, Haili Qi, Mona D. Gundersen, Hang Yang, Ingrid Christiansen, Sveinung W. Sørbye, Rasmus Goll, Jon Florholmen

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 2/2015

Einloggen, um Zugang zu erhalten

Abstract

Most sporadic colorectal cancers (CRCs) develop from preformed adenomas. Cytokines are involved in the transition from adenoma to CRC. Interleukin-33 (IL-33) is a newly discovered proinflammatory cytokine belonging to the IL-1 cytokine family and involved in the development of chronic inflammation and cancer. The aim of this study was to evaluate the dynamics of the IL-33/ST2 axis during the sequence of progression from normal colorectum to adenoma to carcinoma and to investigate the association of IL-33 and ST2 expression with clinicopathological parameters and prognosis. The results demonstrated that the levels of IL-33 and ST2 in adenomas (n = 50), determined by real-time PCR, were significantly higher than those of normal controls (n = 30); the levels of both IL-33/ST mRNA in CRCs (n = 50) were higher than in normal controls but lower than in adenomas. Further analysis revealed that the expression level of ST2 in CRCs was associated with tumor/node/metastasis (TNM) stage. The log-rank test showed that neither the IL-33 nor the ST2 expression level was correlated with overall survival in patients with CRC. The increased expression of IL-33/ST2 in adenomas and CRC tissues was confirmed by immunohistochemistry and was observed in both the tumor stromal cells and adenomatous/cancerous cells. Notably, increased densities of IL-33-positive and ST2-positive microvessels were found in the stroma of adenomas and CRCs. In conclusion, increased expression of the IL-33/ST2 axis along the colorectal adenoma–carcinoma sequence might be involved in the neoplastic transformation via the participation of this axis in the regulation of angiogenesis.
Literatur
1.
Zurück zum Zitat Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61:759–767PubMedCrossRef Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61:759–767PubMedCrossRef
2.
Zurück zum Zitat Leslie A, Carey FA, Pratt NR, Steele RJ (2002) The colorectal adenoma-carcinoma sequence. Br J Surg 89:845–860PubMedCrossRef Leslie A, Carey FA, Pratt NR, Steele RJ (2002) The colorectal adenoma-carcinoma sequence. Br J Surg 89:845–860PubMedCrossRef
4.
5.
Zurück zum Zitat Cacev T, Radosevic S, Krizanac S, Kapitanovic S (2008) Influence of interleukin-8 and interleukin-10 on sporadic colon cancer development and progression. Carcinogenesis 29:1572–1580PubMedCrossRef Cacev T, Radosevic S, Krizanac S, Kapitanovic S (2008) Influence of interleukin-8 and interleukin-10 on sporadic colon cancer development and progression. Carcinogenesis 29:1572–1580PubMedCrossRef
6.
Zurück zum Zitat Waugh DJ, Wilson C (2008) The interleukin-8 pathway in cancer. Clin Cancer Res 14:6735–6741PubMedCrossRef Waugh DJ, Wilson C (2008) The interleukin-8 pathway in cancer. Clin Cancer Res 14:6735–6741PubMedCrossRef
7.
Zurück zum Zitat Fantini MC, Pallone F (2008) Cytokines: from gut inflammation to colorectal cancer. Curr Drug Targets 9:375–380PubMedCrossRef Fantini MC, Pallone F (2008) Cytokines: from gut inflammation to colorectal cancer. Curr Drug Targets 9:375–380PubMedCrossRef
8.
Zurück zum Zitat Choi JW, Liu H, Shin DH, Yu GI, Hwang JS, Kim ES, Yun JW (2013) Proteomic and cytokine plasma biomarkers for predicting progression from colorectal adenoma to carcinoma in human patients. Proteomics 13:2361–2374PubMedCrossRef Choi JW, Liu H, Shin DH, Yu GI, Hwang JS, Kim ES, Yun JW (2013) Proteomic and cytokine plasma biomarkers for predicting progression from colorectal adenoma to carcinoma in human patients. Proteomics 13:2361–2374PubMedCrossRef
9.
Zurück zum Zitat Chung YC, Chang YF (2003) Significance of inflammatory cytokines in the progression of colorectal cancer. Hepatogastroenterology 50:1910–1913PubMed Chung YC, Chang YF (2003) Significance of inflammatory cytokines in the progression of colorectal cancer. Hepatogastroenterology 50:1910–1913PubMed
10.
Zurück zum Zitat Kang M, Edmundson P, Araujo-Perez F, McCoy AN, Galanko J, Keku TO (2013) Association of plasma endotoxin, inflammatory cytokines and risk of colorectal adenomas. BMC Cancer 13:91PubMedCentralPubMedCrossRef Kang M, Edmundson P, Araujo-Perez F, McCoy AN, Galanko J, Keku TO (2013) Association of plasma endotoxin, inflammatory cytokines and risk of colorectal adenomas. BMC Cancer 13:91PubMedCentralPubMedCrossRef
11.
Zurück zum Zitat Kim S, Keku TO, Martin C, Galanko J, Woosley JT, Schroeder JC, Satia JA, Halabi S, Sandler RS (2008) Circulating levels of inflammatory cytokines and risk of colorectal adenomas. Cancer Res 68:323–328PubMedCentralPubMedCrossRef Kim S, Keku TO, Martin C, Galanko J, Woosley JT, Schroeder JC, Satia JA, Halabi S, Sandler RS (2008) Circulating levels of inflammatory cytokines and risk of colorectal adenomas. Cancer Res 68:323–328PubMedCentralPubMedCrossRef
12.
Zurück zum Zitat Krzystek-Korpacka M, Diakowska D, Kapturkiewicz B, Bebenek M, Gamian A (2013) Profiles of circulating inflammatory cytokines in colorectal cancer (CRC), high cancer risk conditions, and health are distinct. Possible implications for CRC screening and surveillance. Cancer Lett 337:107–114PubMedCrossRef Krzystek-Korpacka M, Diakowska D, Kapturkiewicz B, Bebenek M, Gamian A (2013) Profiles of circulating inflammatory cytokines in colorectal cancer (CRC), high cancer risk conditions, and health are distinct. Possible implications for CRC screening and surveillance. Cancer Lett 337:107–114PubMedCrossRef
13.
Zurück zum Zitat Cui G, Goll R, Olsen T, Steigen SE, Husebekk A, Vonen B, Florholmen J (2007) Reduced expression of microenvironmental Th1 cytokines accompanies adenomas-carcinomas sequence of colorectum. Cancer Immunol Immunother 56:985–995PubMedCrossRef Cui G, Goll R, Olsen T, Steigen SE, Husebekk A, Vonen B, Florholmen J (2007) Reduced expression of microenvironmental Th1 cytokines accompanies adenomas-carcinomas sequence of colorectum. Cancer Immunol Immunother 56:985–995PubMedCrossRef
14.
Zurück zum Zitat Cui G, Yuan A, Goll R, Vonen B, Florholmen J (2009) Dynamic changes of interleukin-8 network along the colorectal adenoma-carcinoma sequence. Cancer Immunol Immunother 58:1897–1905PubMedCrossRef Cui G, Yuan A, Goll R, Vonen B, Florholmen J (2009) Dynamic changes of interleukin-8 network along the colorectal adenoma-carcinoma sequence. Cancer Immunol Immunother 58:1897–1905PubMedCrossRef
15.
Zurück zum Zitat Oliveira Frick V, Rubie C, Ghadjar P, Faust SK, Wagner M, Graber S, Schilling MK (2011) Changes in CXCL12/CXCR4-chemokine expression during onset of colorectal malignancies. Tumour Biol 32:189–196PubMedCrossRef Oliveira Frick V, Rubie C, Ghadjar P, Faust SK, Wagner M, Graber S, Schilling MK (2011) Changes in CXCL12/CXCR4-chemokine expression during onset of colorectal malignancies. Tumour Biol 32:189–196PubMedCrossRef
16.
Zurück zum Zitat Pellegrini P, Berghella AM, Contasta I, Del Beato T, Adorno D (2006) The study of a patient’s immune system may prove to be a useful noninvasive tool for stage classification in colon cancer. Cancer Biother Radiopharm 21:443–467PubMedCrossRef Pellegrini P, Berghella AM, Contasta I, Del Beato T, Adorno D (2006) The study of a patient’s immune system may prove to be a useful noninvasive tool for stage classification in colon cancer. Cancer Biother Radiopharm 21:443–467PubMedCrossRef
18.
Zurück zum Zitat Beltran CJ, Nunez LE, Diaz-Jimenez D, Farfan N, Candia E, Heine C, Lopez F, Gonzalez MJ, Quera R, Hermoso MA (2010) Characterization of the novel ST2/IL-33 system in patients with inflammatory bowel disease. Inflamm Bowel Dis 16:1097–1107PubMedCrossRef Beltran CJ, Nunez LE, Diaz-Jimenez D, Farfan N, Candia E, Heine C, Lopez F, Gonzalez MJ, Quera R, Hermoso MA (2010) Characterization of the novel ST2/IL-33 system in patients with inflammatory bowel disease. Inflamm Bowel Dis 16:1097–1107PubMedCrossRef
19.
Zurück zum Zitat Milovanovic M, Volarevic V, Radosavljevic G, Jovanovic I, Pejnovic N, Arsenijevic N, Lukic ML (2012) IL-33/ST2 axis in inflammation and immunopathology. Immunol Res 52:89–99PubMedCrossRef Milovanovic M, Volarevic V, Radosavljevic G, Jovanovic I, Pejnovic N, Arsenijevic N, Lukic ML (2012) IL-33/ST2 axis in inflammation and immunopathology. Immunol Res 52:89–99PubMedCrossRef
20.
Zurück zum Zitat Kobori A, Yagi Y, Imaeda H, Ban H, Bamba S, Tsujikawa T, Saito Y, Fujiyama Y, Andoh A (2010) Interleukin-33 expression is specifically enhanced in inflamed mucosa of ulcerative colitis. J Gastroenterol 45:999–1007PubMedCrossRef Kobori A, Yagi Y, Imaeda H, Ban H, Bamba S, Tsujikawa T, Saito Y, Fujiyama Y, Andoh A (2010) Interleukin-33 expression is specifically enhanced in inflamed mucosa of ulcerative colitis. J Gastroenterol 45:999–1007PubMedCrossRef
21.
Zurück zum Zitat Jovanovic IP, Pejnovic NN, Radosavljevic GD, Arsenijevic NN, Lukic ML (2012) IL-33/ST2 axis in innate and acquired immunity to tumors. Oncoimmunology 1:229–231PubMedCentralPubMedCrossRef Jovanovic IP, Pejnovic NN, Radosavljevic GD, Arsenijevic NN, Lukic ML (2012) IL-33/ST2 axis in innate and acquired immunity to tumors. Oncoimmunology 1:229–231PubMedCentralPubMedCrossRef
22.
Zurück zum Zitat Eiwegger T, Akdis CA (2011) IL-33 links tissue cells, dendritic cells and Th2 cell development in a mouse model of asthma. Eur J Immunol 41:1535–1538PubMedCrossRef Eiwegger T, Akdis CA (2011) IL-33 links tissue cells, dendritic cells and Th2 cell development in a mouse model of asthma. Eur J Immunol 41:1535–1538PubMedCrossRef
23.
Zurück zum Zitat Schmieder A, Multhoff G, Radons J (2012) Interleukin-33 acts as a pro-inflammatory cytokine and modulates its receptor gene expression in highly metastatic human pancreatic carcinoma cells. Cytokine 60:514–521PubMedCrossRef Schmieder A, Multhoff G, Radons J (2012) Interleukin-33 acts as a pro-inflammatory cytokine and modulates its receptor gene expression in highly metastatic human pancreatic carcinoma cells. Cytokine 60:514–521PubMedCrossRef
24.
Zurück zum Zitat Chen SF, Nieh S, Jao SW, Wu MZ, Liu CL, Chang YC, Lin YS (2013) The paracrine effect of cancer-associated fibroblast-induced interleukin-33 regulates the invasiveness of head and neck squamous cell carcinoma. J Pathol 231:180–189PubMedCrossRef Chen SF, Nieh S, Jao SW, Wu MZ, Liu CL, Chang YC, Lin YS (2013) The paracrine effect of cancer-associated fibroblast-induced interleukin-33 regulates the invasiveness of head and neck squamous cell carcinoma. J Pathol 231:180–189PubMedCrossRef
25.
Zurück zum Zitat Zhang P, Liu XK, Chu Z, Ye JC, Li KL, Zhuang WL, Yang DJ, Jiang YF (2012) Detection of interleukin-33 in serum and carcinoma tissue from patients with hepatocellular carcinoma and its clinical implications. J Int Med Res 40:1654–1661PubMedCrossRef Zhang P, Liu XK, Chu Z, Ye JC, Li KL, Zhuang WL, Yang DJ, Jiang YF (2012) Detection of interleukin-33 in serum and carcinoma tissue from patients with hepatocellular carcinoma and its clinical implications. J Int Med Res 40:1654–1661PubMedCrossRef
26.
Zurück zum Zitat Hu LA, Fu Y, Zhang DN, Zhang J (2013) Serum IL-33 as a diagnostic and prognostic marker in non- small cell lung cancer. Asian Pac J Cancer Prev 14:2563–2566PubMedCrossRef Hu LA, Fu Y, Zhang DN, Zhang J (2013) Serum IL-33 as a diagnostic and prognostic marker in non- small cell lung cancer. Asian Pac J Cancer Prev 14:2563–2566PubMedCrossRef
27.
Zurück zum Zitat Sun P, Ben Q, Tu S, Dong W, Qi X, Wu Y (2011) Serum interleukin-33 levels in patients with gastric cancer. Dig Dis Sci 56:3596–3601PubMedCrossRef Sun P, Ben Q, Tu S, Dong W, Qi X, Wu Y (2011) Serum interleukin-33 levels in patients with gastric cancer. Dig Dis Sci 56:3596–3601PubMedCrossRef
28.
Zurück zum Zitat Musolino C, Allegra A, Profita M, Alonci A, Saitta S, Russo S, Bonanno A, Innao V, Gangemi S (2013) Reduced IL-33 plasma levels in multiple myeloma patients are associated with more advanced stage of disease. Br J Heamatol 160:709–710CrossRef Musolino C, Allegra A, Profita M, Alonci A, Saitta S, Russo S, Bonanno A, Innao V, Gangemi S (2013) Reduced IL-33 plasma levels in multiple myeloma patients are associated with more advanced stage of disease. Br J Heamatol 160:709–710CrossRef
29.
Zurück zum Zitat Seidelin JB, Rogler G, Nielsen OH (2011) A role for interleukin-33 in T(H)2-polarized intestinal inflammation? Mucosal Immunol 4:496–502PubMedCrossRef Seidelin JB, Rogler G, Nielsen OH (2011) A role for interleukin-33 in T(H)2-polarized intestinal inflammation? Mucosal Immunol 4:496–502PubMedCrossRef
30.
Zurück zum Zitat Cui G, Olsen T, Christiansen I, Vonen B, Florholmen J, Goll R (2006) Improvement of real-time polymerase chain reaction for quantifying TNF-alpha mRNA expression in inflamed colorectal mucosa: an approach to optimize procedures for clinical use. Scand J Clin Lab Inv 66:249–259CrossRef Cui G, Olsen T, Christiansen I, Vonen B, Florholmen J, Goll R (2006) Improvement of real-time polymerase chain reaction for quantifying TNF-alpha mRNA expression in inflamed colorectal mucosa: an approach to optimize procedures for clinical use. Scand J Clin Lab Inv 66:249–259CrossRef
31.
Zurück zum Zitat Cui G, Koh TJ, Chen D, Zhao CM, Takaishi S, Dockray GJ, Varro A, Rogers AB, Fox JG, Wang TC (2004) Overexpression of glycine-extended gastrin inhibits parietal cell loss and atrophy in the mouse stomach. Cancer Res 64:8160–8166PubMedCrossRef Cui G, Koh TJ, Chen D, Zhao CM, Takaishi S, Dockray GJ, Varro A, Rogers AB, Fox JG, Wang TC (2004) Overexpression of glycine-extended gastrin inhibits parietal cell loss and atrophy in the mouse stomach. Cancer Res 64:8160–8166PubMedCrossRef
32.
Zurück zum Zitat Cui J, Xu G, Liu J, Pang Z, Florholmen J, Cui G (2013) The expression of non-mast histamine in tumor associated microvessels in human colorectal cancers. Pathol Oncol Res 19:311–316PubMedCrossRef Cui J, Xu G, Liu J, Pang Z, Florholmen J, Cui G (2013) The expression of non-mast histamine in tumor associated microvessels in human colorectal cancers. Pathol Oncol Res 19:311–316PubMedCrossRef
33.
Zurück zum Zitat Jovanovic IP, Pejnovic NN, Radosavljevic GD, Pantic JM, Milovanovic MZ, Arsenijevic NN, Lukic ML (2014) Interleukin-33/ST2 axis promotes breast cancer growth and metastases by facilitating intratumoral accumulation of immunosuppressive and innate lymphoid cells. Int J Cancer 134:1669–1682PubMedCrossRef Jovanovic IP, Pejnovic NN, Radosavljevic GD, Pantic JM, Milovanovic MZ, Arsenijevic NN, Lukic ML (2014) Interleukin-33/ST2 axis promotes breast cancer growth and metastases by facilitating intratumoral accumulation of immunosuppressive and innate lymphoid cells. Int J Cancer 134:1669–1682PubMedCrossRef
34.
Zurück zum Zitat Kuchler AM, Pollheimer J, Balogh J, Sponheim J, Manley L, Sorensen DR, De Angelis PM, Scott H, Haraldsen G (2008) Nuclear interleukin-33 is generally expressed in resting endothelium but rapidly lost upon angiogenic or proinflammatory activation. Am J Pathol 173:1229–1242PubMedCentralPubMedCrossRef Kuchler AM, Pollheimer J, Balogh J, Sponheim J, Manley L, Sorensen DR, De Angelis PM, Scott H, Haraldsen G (2008) Nuclear interleukin-33 is generally expressed in resting endothelium but rapidly lost upon angiogenic or proinflammatory activation. Am J Pathol 173:1229–1242PubMedCentralPubMedCrossRef
35.
Zurück zum Zitat Contasta I, Berghella AM, Pellegrini P, Adorno D (2003) Passage from normal mucosa to adenoma and colon cancer: alteration of normal sCD30 mechanisms regulating TH1/TH2 cell functions. Cancer Biother Radiopharm 18:549–557PubMedCrossRef Contasta I, Berghella AM, Pellegrini P, Adorno D (2003) Passage from normal mucosa to adenoma and colon cancer: alteration of normal sCD30 mechanisms regulating TH1/TH2 cell functions. Cancer Biother Radiopharm 18:549–557PubMedCrossRef
36.
Zurück zum Zitat Marvie P, Lisbonne M, L’Helgoualc’h A, Rauch M, Turlin B, Preisser L, Bourd-Boittin K, Theret N, Gascan H, Piquet-Pellorce C, Samson M (2010) Interleukin-33 overexpression is associated with liver fibrosis in mice and humans. J Cell Mol Med 14:1726–1739PubMedCrossRef Marvie P, Lisbonne M, L’Helgoualc’h A, Rauch M, Turlin B, Preisser L, Bourd-Boittin K, Theret N, Gascan H, Piquet-Pellorce C, Samson M (2010) Interleukin-33 overexpression is associated with liver fibrosis in mice and humans. J Cell Mol Med 14:1726–1739PubMedCrossRef
37.
Zurück zum Zitat Meephansan J, Tsuda H, Komine M, Tominaga S, Ohtsuki M (2012) Regulation of IL-33 expression by IFN-gamma and tumor necrosis factor-alpha in normal human epidermal keratinocytes. J Invest Dermatol 132:2593–2600PubMedCrossRef Meephansan J, Tsuda H, Komine M, Tominaga S, Ohtsuki M (2012) Regulation of IL-33 expression by IFN-gamma and tumor necrosis factor-alpha in normal human epidermal keratinocytes. J Invest Dermatol 132:2593–2600PubMedCrossRef
38.
Zurück zum Zitat Byrne SN, Beaugie C, O’Sullivan C, Leighton S, Halliday GM (2011) The immune-modulating cytokine and endogenous Alarmin interleukin-33 is upregulated in skin exposed to inflammatory UVB radiation. Am J Pathol 179:211–222PubMedCentralPubMedCrossRef Byrne SN, Beaugie C, O’Sullivan C, Leighton S, Halliday GM (2011) The immune-modulating cytokine and endogenous Alarmin interleukin-33 is upregulated in skin exposed to inflammatory UVB radiation. Am J Pathol 179:211–222PubMedCentralPubMedCrossRef
39.
Zurück zum Zitat Seltmann J, Werfel T, Wittmann M (2013) Evidence for a regulatory loop between IFN-gamma and IL-33 in skin inflammation. Exp Dermatol 22:102–107PubMedCrossRef Seltmann J, Werfel T, Wittmann M (2013) Evidence for a regulatory loop between IFN-gamma and IL-33 in skin inflammation. Exp Dermatol 22:102–107PubMedCrossRef
40.
Zurück zum Zitat Gschwantler M, Kriwanek S, Langner E, Goritzer B, Schrutka-Kolbl C, Brownstone E, Feichtinger H, Weiss W (2002) High-grade dysplasia and invasive carcinoma in colorectal adenomas: a multivariate analysis of the impact of adenoma and patient characteristics. Eur J Gastroenterol Hepatol 14:183–188PubMedCrossRef Gschwantler M, Kriwanek S, Langner E, Goritzer B, Schrutka-Kolbl C, Brownstone E, Feichtinger H, Weiss W (2002) High-grade dysplasia and invasive carcinoma in colorectal adenomas: a multivariate analysis of the impact of adenoma and patient characteristics. Eur J Gastroenterol Hepatol 14:183–188PubMedCrossRef
41.
Zurück zum Zitat Ajdukovic J, Tonkic A, Salamunic I, Hozo I, Simunic M, Bonacin D (2010) Interleukins IL-33 and IL-17/IL-17A in patients with ulcerative colitis. Hepatogastroenterology 57:1442–1444PubMed Ajdukovic J, Tonkic A, Salamunic I, Hozo I, Simunic M, Bonacin D (2010) Interleukins IL-33 and IL-17/IL-17A in patients with ulcerative colitis. Hepatogastroenterology 57:1442–1444PubMed
42.
Zurück zum Zitat Seidelin JB, Bjerrum JT, Coskun M, Widjaya B, Vainer B, Nielsen OH (2010) IL-33 is upregulated in colonocytes of ulcerative colitis. Immunol Lett 128:80–85PubMedCrossRef Seidelin JB, Bjerrum JT, Coskun M, Widjaya B, Vainer B, Nielsen OH (2010) IL-33 is upregulated in colonocytes of ulcerative colitis. Immunol Lett 128:80–85PubMedCrossRef
43.
Zurück zum Zitat Choi YS, Choi HJ, Min JK, Pyun BJ, Maeng YS, Park H, Kim J, Kim YM, Kwon YG (2009) Interleukin-33 induces angiogenesis and vascular permeability through ST2/TRAF6-mediated endothelial nitric oxide production. Blood 114:3117–3126PubMedCrossRef Choi YS, Choi HJ, Min JK, Pyun BJ, Maeng YS, Park H, Kim J, Kim YM, Kwon YG (2009) Interleukin-33 induces angiogenesis and vascular permeability through ST2/TRAF6-mediated endothelial nitric oxide production. Blood 114:3117–3126PubMedCrossRef
Metadaten
Titel
Dynamics of the IL-33/ST2 network in the progression of human colorectal adenoma to sporadic colorectal cancer
verfasst von
Guanglin Cui
Haili Qi
Mona D. Gundersen
Hang Yang
Ingrid Christiansen
Sveinung W. Sørbye
Rasmus Goll
Jon Florholmen
Publikationsdatum
01.02.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
Cancer Immunology, Immunotherapy / Ausgabe 2/2015
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-014-1624-x

Weitere Artikel der Ausgabe 2/2015

Cancer Immunology, Immunotherapy 2/2015 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.