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Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Research article

Serum soluble ST2 is associated with ER-positive breast cancer

Authors: Da-peng Lu, Xiang-yu Zhou, Lu-tian Yao, Cai-gang Liu, Wei Ma, Feng Jin, Yun-fei Wu

Published in: BMC Cancer | Issue 1/2014

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Abstract

Background

ST2, a member of the interleukin (IL)-1receptor family, regulates Th1/Th2 immune responses in autoimmune and inflammatory conditions. However, the role of ST2 signaling in tumor growth and metastasis of breast cancers has not been investigated. This study investigated the possible role of soluble ST2 (sST2) in breast cancer.

Methods

The serum levels of IL-33, sST2, and vascular endothelial growth factor (VEGF) in 150 breast cancer patients and 90 healthy women were measured by enzyme-linked immunosorbent assay. Estrogen receptor(ER), progesterone receptor, human epithelial receptor (HER)-2, and cell cycle regulated protein Ki-67 were measured. Clinical stage, tumor size, lymph node metastasis, and histological type were also recorded.

Results

The serum levels of sST2, IL-33, and VEGF were significantly higher in breast cancer patients than in the control group (P < 0.05, each). Serum sST2 levels in ER-positive breast cancer patients were significantly associated with age, histological type, clinical stage, tumor size, and Ki-67 status (P < 0.05, each). Moreover, the serum levels of IL-33 and sST2 in breast cancers significantly correlated with VEGF levels (IL-33: r = 0.375, P < 0.0001; sST2: r = 0.164, P = 0.045). Serum levels of sST2, IL-33, and VEGF decreased after modified radical mastectomy in ER-positive breast cancers. Serum levels of IL-33, sST2, and VEGF and clinicopathological factors were not significantly correlated with disease-free survival and overall survival of ER-positive breast cancer women during follow-up.

Conclusion

Serum sST2 levels in ER-positive breast cancer patients are significantly associated with factors that indicate poor prognosis.
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Literature
1.
go back to reference Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin. 2011, 61 (2): 69-90. 10.3322/caac.20107.CrossRefPubMed Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA Cancer J Clin. 2011, 61 (2): 69-90. 10.3322/caac.20107.CrossRefPubMed
2.
go back to reference Xiang M, Zhou W, Gao D, Fang X, Liu Q: Inhibitor of Apoptosis Protein-Like Protein-2 as a Novel Serological Biomarker for Breast Cancer. Int J Mol Sci. 2012, 13 (12): 16737-16750. 10.3390/ijms131216737.CrossRefPubMedPubMedCentral Xiang M, Zhou W, Gao D, Fang X, Liu Q: Inhibitor of Apoptosis Protein-Like Protein-2 as a Novel Serological Biomarker for Breast Cancer. Int J Mol Sci. 2012, 13 (12): 16737-16750. 10.3390/ijms131216737.CrossRefPubMedPubMedCentral
3.
go back to reference Klemenz R, Hoffmann S, Werenskiold AK: Serum- and oncoprotein-mediated induction of a gene with sequence similarity to the gene encoding carcinoembryonic antigen. Proc Natl Acad Sci USA. 1989, 86 (15): 5708-5712. 10.1073/pnas.86.15.5708.CrossRefPubMedPubMedCentral Klemenz R, Hoffmann S, Werenskiold AK: Serum- and oncoprotein-mediated induction of a gene with sequence similarity to the gene encoding carcinoembryonic antigen. Proc Natl Acad Sci USA. 1989, 86 (15): 5708-5712. 10.1073/pnas.86.15.5708.CrossRefPubMedPubMedCentral
4.
go back to reference Tago K, Noda T, Hayakawa M, Iwahana H, Yanagisawa K, Yashiro T, Tominaga S: Tissue distribution and subcellular localization of a variant form of the human ST2 gene product, ST2V. Biochem Biophys Res Commun. 2001, 285: 1377-13834. 10.1006/bbrc.2001.5306.CrossRefPubMed Tago K, Noda T, Hayakawa M, Iwahana H, Yanagisawa K, Yashiro T, Tominaga S: Tissue distribution and subcellular localization of a variant form of the human ST2 gene product, ST2V. Biochem Biophys Res Commun. 2001, 285: 1377-13834. 10.1006/bbrc.2001.5306.CrossRefPubMed
5.
go back to reference Liew FY, Pitman NI, McInnes IB: Disease-associated function of IL-33: the new kid in the IL-1 family. Nat Rev Immunol. 2010, 10 (2): 103-110. 10.1038/nri2692.CrossRefPubMed Liew FY, Pitman NI, McInnes IB: Disease-associated function of IL-33: the new kid in the IL-1 family. Nat Rev Immunol. 2010, 10 (2): 103-110. 10.1038/nri2692.CrossRefPubMed
6.
go back to reference Choi YS, Choi HJ, Min JK, Pyun BJ, Maeng YS, Park H, Kim J, Kim YM, Kwon YG: Interleukin-33 induces angiogenesis and vascular permeability through ST2/TRAF6-mediated endothelial nitric oxide production. Blood. 2009, 114 (14): 3117-3126. 10.1182/blood-2009-02-203372.CrossRefPubMed Choi YS, Choi HJ, Min JK, Pyun BJ, Maeng YS, Park H, Kim J, Kim YM, Kwon YG: Interleukin-33 induces angiogenesis and vascular permeability through ST2/TRAF6-mediated endothelial nitric oxide production. Blood. 2009, 114 (14): 3117-3126. 10.1182/blood-2009-02-203372.CrossRefPubMed
7.
go back to reference Miller AM, Liew FY: The IL-33/ST2 pathway--A new therapeutic target in cardiovascular disease. Pharmacol Ther. 2011, 131 (2): 179-186. 10.1016/j.pharmthera.2011.02.005.CrossRefPubMed Miller AM, Liew FY: The IL-33/ST2 pathway--A new therapeutic target in cardiovascular disease. Pharmacol Ther. 2011, 131 (2): 179-186. 10.1016/j.pharmthera.2011.02.005.CrossRefPubMed
8.
go back to reference Schmieder A, Multhoff G, Radons J: Interleukin-33 acts as a pro-inflammatory cytokine and modulates its receptor gene expression in highly metastatic human pancreatic carcinoma cells. Cytokine. 2012, 60 (2): 514-521. 10.1016/j.cyto.2012.06.286.CrossRefPubMed Schmieder A, Multhoff G, Radons J: Interleukin-33 acts as a pro-inflammatory cytokine and modulates its receptor gene expression in highly metastatic human pancreatic carcinoma cells. Cytokine. 2012, 60 (2): 514-521. 10.1016/j.cyto.2012.06.286.CrossRefPubMed
9.
go back to reference Jovanovic I, Radosavljevic G, Mitrovic M, Juranic VL, McKenzie AN, Arsenijevic N, Jonjic S, Lukic ML: ST2 deletion enhances innate and acquired immunity to murine mammary carcinoma. Eur J Immunol. 2011, 41 (7): 1902-1912. 10.1002/eji.201141417.CrossRefPubMedPubMedCentral Jovanovic I, Radosavljevic G, Mitrovic M, Juranic VL, McKenzie AN, Arsenijevic N, Jonjic S, Lukic ML: ST2 deletion enhances innate and acquired immunity to murine mammary carcinoma. Eur J Immunol. 2011, 41 (7): 1902-1912. 10.1002/eji.201141417.CrossRefPubMedPubMedCentral
10.
go back to reference Carlson RW, Allred DC, Anderson BO, Burstein HJ, Edge SB, Farrar WB, Forero A, Giordano SH, Goldstein LJ, Gradishar WJ, Hayes DF, Hudis CA, Isakoff SJ, Ljung BM, Mankoff DA, Marcom PK, Mayer IA, McCormick B, Pierce LJ, Reed EC, Smith ML, Soliman H, Somlo G, Theriault RL, Ward JH, Wolff AC, Zellars R, Kumar R, Shead DA: National comprehensive cancer network. J Natl Compr Canc Netw. 2012, 10 (7): 821-829.PubMedPubMedCentral Carlson RW, Allred DC, Anderson BO, Burstein HJ, Edge SB, Farrar WB, Forero A, Giordano SH, Goldstein LJ, Gradishar WJ, Hayes DF, Hudis CA, Isakoff SJ, Ljung BM, Mankoff DA, Marcom PK, Mayer IA, McCormick B, Pierce LJ, Reed EC, Smith ML, Soliman H, Somlo G, Theriault RL, Ward JH, Wolff AC, Zellars R, Kumar R, Shead DA: National comprehensive cancer network. J Natl Compr Canc Netw. 2012, 10 (7): 821-829.PubMedPubMedCentral
11.
go back to reference Gillibert-Duplantier J, Duthey B, Sisirak V, Salaün D, Gargi T, Trédan O, Finetti P, Bertucci F, Birnbaum D, Bendriss-Vermare N, Badache A: Gene expression profiling identifies sST2 as an effector of ErbB2-driven breast carcinoma ellmotility, associated with metastasis. Oncogene. 2012, 31 (30): 3516-3524. 10.1038/onc.2011.525.CrossRefPubMed Gillibert-Duplantier J, Duthey B, Sisirak V, Salaün D, Gargi T, Trédan O, Finetti P, Bertucci F, Birnbaum D, Bendriss-Vermare N, Badache A: Gene expression profiling identifies sST2 as an effector of ErbB2-driven breast carcinoma ellmotility, associated with metastasis. Oncogene. 2012, 31 (30): 3516-3524. 10.1038/onc.2011.525.CrossRefPubMed
12.
go back to reference Küchler AM, Pollheimer J, Balogh J, Sponheim J, Manley L, Sorensen DR, De Angelis PM, Scott H, Haraldsen G: Nuclear interleukin-33 is generally expressed in resting endothelium but rapidly lost upon angiogenicor proinflammatory activation. Am J Pathol. 2008, 173 (4): 1229-1242. 10.2353/ajpath.2008.080014.CrossRefPubMedPubMedCentral Küchler AM, Pollheimer J, Balogh J, Sponheim J, Manley L, Sorensen DR, De Angelis PM, Scott H, Haraldsen G: Nuclear interleukin-33 is generally expressed in resting endothelium but rapidly lost upon angiogenicor proinflammatory activation. Am J Pathol. 2008, 173 (4): 1229-1242. 10.2353/ajpath.2008.080014.CrossRefPubMedPubMedCentral
13.
go back to reference Dunnwald LK, Rossing MA, Li CI: Hormone receptor status, tumor characteristics, and prognosis: a prospective cohort of breast cancer patients. Breast Cancer Res. 2007, 9 (1): R6-10.1186/bcr1639.CrossRefPubMedPubMedCentral Dunnwald LK, Rossing MA, Li CI: Hormone receptor status, tumor characteristics, and prognosis: a prospective cohort of breast cancer patients. Breast Cancer Res. 2007, 9 (1): R6-10.1186/bcr1639.CrossRefPubMedPubMedCentral
14.
go back to reference Sahin AA, Ro J, Ro JY, Blick MB, el-Naggar AK, Ordonez NG, Fritsche HA, Smith TL, Hortobagyi GN, Ayala AG: Ki-67 immunostaining in node-negative stage I/II breast carcinoma. Significant correlation with prognosis. Cancer. 1991, 68 (3): 549-557. 10.1002/1097-0142(19910801)68:3<549::AID-CNCR2820680318>3.0.CO;2-J.CrossRefPubMed Sahin AA, Ro J, Ro JY, Blick MB, el-Naggar AK, Ordonez NG, Fritsche HA, Smith TL, Hortobagyi GN, Ayala AG: Ki-67 immunostaining in node-negative stage I/II breast carcinoma. Significant correlation with prognosis. Cancer. 1991, 68 (3): 549-557. 10.1002/1097-0142(19910801)68:3<549::AID-CNCR2820680318>3.0.CO;2-J.CrossRefPubMed
15.
go back to reference Dvorak HF: Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J Clin Oncol. 2002, 20 (21): 4368-4380. 10.1200/JCO.2002.10.088.CrossRefPubMed Dvorak HF: Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J Clin Oncol. 2002, 20 (21): 4368-4380. 10.1200/JCO.2002.10.088.CrossRefPubMed
16.
go back to reference Heer K, Kumar H, Read JR, Fox JN, Monson JR, Kerin MJ: Serum vascular endothelial growth factor in breast cancer: its relation with cancer type and estrogen receptor status. Clin Cancer Res. 2001, 7: 3491-3494.PubMed Heer K, Kumar H, Read JR, Fox JN, Monson JR, Kerin MJ: Serum vascular endothelial growth factor in breast cancer: its relation with cancer type and estrogen receptor status. Clin Cancer Res. 2001, 7: 3491-3494.PubMed
17.
go back to reference Hodorowicz-Zaniewska D, Kibil W, Małek A, Szpor J, Kulig J, Sztefko K: Evaluation of serum concentrations of vascular endothelial growth factor (VEGF) in breast cancer patients. Pol J Pathol. 2012, 63 (4): 255-260.CrossRefPubMed Hodorowicz-Zaniewska D, Kibil W, Małek A, Szpor J, Kulig J, Sztefko K: Evaluation of serum concentrations of vascular endothelial growth factor (VEGF) in breast cancer patients. Pol J Pathol. 2012, 63 (4): 255-260.CrossRefPubMed
18.
go back to reference Hu Moulin D, Donze O, Talabot-Ayer D, Mezin F, Palmer G, Gabay C: Interleukin (IL)-33 induces the release of pro-inflammatory mediators by mast cells. Cytokine. 2007, 40 (3): 216-225. 10.1016/j.cyto.2007.09.013.CrossRef Hu Moulin D, Donze O, Talabot-Ayer D, Mezin F, Palmer G, Gabay C: Interleukin (IL)-33 induces the release of pro-inflammatory mediators by mast cells. Cytokine. 2007, 40 (3): 216-225. 10.1016/j.cyto.2007.09.013.CrossRef
Metadata
Title
Serum soluble ST2 is associated with ER-positive breast cancer
Authors
Da-peng Lu
Xiang-yu Zhou
Lu-tian Yao
Cai-gang Liu
Wei Ma
Feng Jin
Yun-fei Wu
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-198

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