Skip to main content
Top
Published in: Journal of Cancer Research and Clinical Oncology 6/2010

01-06-2010 | Original Paper

Expression of IL-13Rα2 in liver cancer cells and its effect on targeted therapy of liver cancer

Authors: Lingling Hou, Juan Du, Jianwei Wang, Yanfeng Liu, Weimin Sun, Yanpeng Zheng, Lishu Zhang, Honggang Hu, Xinxian Dai, Weijun Guan, Yuehui Ma, Tao Hong

Published in: Journal of Cancer Research and Clinical Oncology | Issue 6/2010

Login to get access

Abstract

Purpose

Liver cancer is the third leading cause of cancer-related deaths globally. The number of liver cancers diagnosed in the world is increasing at an alarming rate. It is of great significance to find the new targets of the tumor cells and specific medicine. This research investigated the expression of interleukin-13 receptor α2 (IL-13Rα2) in different liver cancer cell lines and liver cancer tissues, and assessed the cytotoxin DT389-hIL13-13E13K (IL-13 and diphtheria toxin fusion protein) targeted killing effect on liver cancer cells. Based on study above, we further analyzed the function of IL-13Rα2 on the targeted liver cancer therapy. The results will provide a novel strategy and an alternative way for liver cancer therapy.

Methods

The expression of IL-13Rα2 in different liver cancer cell lines and tissues were analyzed by RT-PCR and immunohistochemistry. Cytotoxicity assay of DT389-hIL13-13E13K was performed in eight different concentrations in liver cancer cell lines in vitro. At the same time, siRNA-mediated knockdown was introduced to assess the role of IL-13Rα2 in liver cancer therapy.

Results

Two out of four tested liver cancer cell lines and 27 out of 33 (81.82%) liver tissues expressed the IL-13Rα2. The fusion protein DT389-hIL13-13E13K showed a moderate cytotoxicity to the cancer cell line BEL-7402 in vitro, which 50% inhibition (IC50) concentration occurred at 1.4 × 10−5 M. Besides, the sensitivity to fusion protein DT389-hIL13-13E13K was decreased in siRNA-transfected liver cells compared with control ones. These results suggest that IL-13Rα2 chain is a specific target for IL-13-directed fusion protein.

Conclusions

We reported the expression of IL-13Rα2 in liver cancer cell lines and tissues as well as investigated the cytotoxin (DT389-hIL13-13E13K) targeted killing efficiency of liver cancer cells and potential role of IL-13Rα2 in the cancer treatment.
Literature
go back to reference Donaldson DD, Whitters MJ, Fitz LJ, Neben TY, Finnerty H, Henderson SL, O’Hara RM Jr, Beier DR, Turner KJ, Wood CR, Collins M (1998) The murine IL-13 receptor a2: molecular cloning, characterization, and comparison with murine IL-13 receptor α1. J Immunol 161:2317–2324PubMed Donaldson DD, Whitters MJ, Fitz LJ, Neben TY, Finnerty H, Henderson SL, O’Hara RM Jr, Beier DR, Turner KJ, Wood CR, Collins M (1998) The murine IL-13 receptor a2: molecular cloning, characterization, and comparison with murine IL-13 receptor α1. J Immunol 161:2317–2324PubMed
go back to reference Du J, Zheng YP, Sun W, Hu HG, Hou LL, Hong T (2008) Targeted killing effect of IL-13 diphtheria toxin fusion protein and DT389-hIL13-13E13K. J Med Res 37(10):31–36 Du J, Zheng YP, Sun W, Hu HG, Hou LL, Hong T (2008) Targeted killing effect of IL-13 diphtheria toxin fusion protein and DT389-hIL13-13E13K. J Med Res 37(10):31–36
go back to reference Fluckiger AC, Brière F, Zurawski G, Bridon JM, Banchereau J (1994) IL-13 has only a subset of IL-4-like activities on B chronic lymphocytic leukaemia cells. Immunology 83(3):397–403PubMed Fluckiger AC, Brière F, Zurawski G, Bridon JM, Banchereau J (1994) IL-13 has only a subset of IL-4-like activities on B chronic lymphocytic leukaemia cells. Immunology 83(3):397–403PubMed
go back to reference Forner A, Hessheimer AJ, Isabel Real M, Bruix J (2006) Treatment of hepatocellular carcinoma. Crit Rev Oncol Hematol 60:89–98CrossRefPubMed Forner A, Hessheimer AJ, Isabel Real M, Bruix J (2006) Treatment of hepatocellular carcinoma. Crit Rev Oncol Hematol 60:89–98CrossRefPubMed
go back to reference Greten TF, Papendorf F, Bleck JS, Kirchhoff T, Wohlberedt T, Kubicka S, Klempnauer J, Galanski M, Manns MP (2005) Survival rate in patients with hepatocellular carcinoma: a retrospective analysis of 389 patients. Br J Cancer 92(10):1862–1868CrossRefPubMed Greten TF, Papendorf F, Bleck JS, Kirchhoff T, Wohlberedt T, Kubicka S, Klempnauer J, Galanski M, Manns MP (2005) Survival rate in patients with hepatocellular carcinoma: a retrospective analysis of 389 patients. Br J Cancer 92(10):1862–1868CrossRefPubMed
go back to reference Husain SR, Puri RK (2000) Interleukin-13 fusion cytotoxin as a potent targeted agent for AIDS-Kaposi’s sarcoma xenograft. Blood 95(11):3506–3513PubMed Husain SR, Puri RK (2000) Interleukin-13 fusion cytotoxin as a potent targeted agent for AIDS-Kaposi’s sarcoma xenograft. Blood 95(11):3506–3513PubMed
go back to reference Jiang J, Nilsson-Ehle P, Xu N (2006) Influence of liver cancer on lipid and lipoprotein metabolism. Lipids Health Dis 5:4CrossRefPubMed Jiang J, Nilsson-Ehle P, Xu N (2006) Influence of liver cancer on lipid and lipoprotein metabolism. Lipids Health Dis 5:4CrossRefPubMed
go back to reference Joshi BH, Plautz GE, Puri RK (2000) Interleukin-13 Receptor α Chain: a novel tumor-associated transmembrane protein in primary explants of human malignant gliomas. Cancer Res 60(5):1168–1172PubMed Joshi BH, Plautz GE, Puri RK (2000) Interleukin-13 Receptor α Chain: a novel tumor-associated transmembrane protein in primary explants of human malignant gliomas. Cancer Res 60(5):1168–1172PubMed
go back to reference Kawakami K, Kawakami M, Sony PJ, Husain SR, Puri RK (2001) In vivo overexpression of IL-13 receptor α2 chain inhibits tumorigenicity of human breast and pancreatic tumors in immunodeficient mice. J Exp Med 194(12):1743–1754CrossRefPubMed Kawakami K, Kawakami M, Sony PJ, Husain SR, Puri RK (2001) In vivo overexpression of IL-13 receptor α2 chain inhibits tumorigenicity of human breast and pancreatic tumors in immunodeficient mice. J Exp Med 194(12):1743–1754CrossRefPubMed
go back to reference Kawakami M, Kawakami K, Kasperbauer JL, Hinkley LL, Tsukuda M, Strome SE, Puri RK (2003) Interleukin-13 receptor α2 chain in human head and neck cancer serves as a unique diagnostic marker. Clin Cancer Res 9(17):6381–6388PubMed Kawakami M, Kawakami K, Kasperbauer JL, Hinkley LL, Tsukuda M, Strome SE, Puri RK (2003) Interleukin-13 receptor α2 chain in human head and neck cancer serves as a unique diagnostic marker. Clin Cancer Res 9(17):6381–6388PubMed
go back to reference Kawakami K, Kawakami M, Puri RK (2004a) Specifically targeted killing of interleukin-13 (IL-13) receptor-expressing breast cancer by IL-13 fusion cytotoxin in animal model of human disease. Mol Cancer Ther 3(2):137–147PubMed Kawakami K, Kawakami M, Puri RK (2004a) Specifically targeted killing of interleukin-13 (IL-13) receptor-expressing breast cancer by IL-13 fusion cytotoxin in animal model of human disease. Mol Cancer Ther 3(2):137–147PubMed
go back to reference Kawakami M, Kawakami K, Takahashi S, Abe M, Puri RK (2004b) Analysis of interleukin-13 receptor α2 expression in human pediatric brain tumors. Cancer 101(5):1036–1042CrossRefPubMed Kawakami M, Kawakami K, Takahashi S, Abe M, Puri RK (2004b) Analysis of interleukin-13 receptor α2 expression in human pediatric brain tumors. Cancer 101(5):1036–1042CrossRefPubMed
go back to reference Kawakami K, Kioi M, Liu Q, Kawakami M, Puri RK (2005) Evidence that IL-13Rα2 chain in human glioma cells is responsible for the antitumor activity mediated by receptor-directed cytotoxin therapy. J Immunother 28(3):193–202CrossRefPubMed Kawakami K, Kioi M, Liu Q, Kawakami M, Puri RK (2005) Evidence that IL-13Rα2 chain in human glioma cells is responsible for the antitumor activity mediated by receptor-directed cytotoxin therapy. J Immunother 28(3):193–202CrossRefPubMed
go back to reference Kioi M, Kawakami K, Puri RK (2004) Analysis of antitumor activity of an interleukin-13 (IL-13) receptor-targeted cytotoxin composed of IL-13 antagonist and pseudomonas exotoxin. Clin Cancer Res 10:6231–6238CrossRefPubMed Kioi M, Kawakami K, Puri RK (2004) Analysis of antitumor activity of an interleukin-13 (IL-13) receptor-targeted cytotoxin composed of IL-13 antagonist and pseudomonas exotoxin. Clin Cancer Res 10:6231–6238CrossRefPubMed
go back to reference Kioi M, Kawakami M, Shimamura T, Husain SR, Puri RK (2006) Interleukin-13 receptor α2 China: a potential biomarker and molecular target for ovarian cancer therapy. Cancer 107(6):1407–1418CrossRefPubMed Kioi M, Kawakami M, Shimamura T, Husain SR, Puri RK (2006) Interleukin-13 receptor α2 China: a potential biomarker and molecular target for ovarian cancer therapy. Cancer 107(6):1407–1418CrossRefPubMed
go back to reference Kioi M, Shimamura T, Nakashima H, Hirota M, Tohnai I, Husain SR, Puri RK (2009) IL-13 cytotoxin has potent antitumor activity and synergizes with paclitaxel in a mouse model of oral squamous cell carcinoma. Int J Cancer 124(6):1440–1448CrossRefPubMed Kioi M, Shimamura T, Nakashima H, Hirota M, Tohnai I, Husain SR, Puri RK (2009) IL-13 cytotoxin has potent antitumor activity and synergizes with paclitaxel in a mouse model of oral squamous cell carcinoma. Int J Cancer 124(6):1440–1448CrossRefPubMed
go back to reference Kunwar S, Chang SM, Prados MD, Berger MS, Sampson JH, Croteau D, Sherman JW, Grahn AY, Shu VS, Dul JL, Husain SR, Joshi BH (2006) Safety of intraparenchymal convection-enhanced delivery of cintredekin besudotox in early-phase studies. Neurosurg Focus 20(4):E15PubMed Kunwar S, Chang SM, Prados MD, Berger MS, Sampson JH, Croteau D, Sherman JW, Grahn AY, Shu VS, Dul JL, Husain SR, Joshi BH (2006) Safety of intraparenchymal convection-enhanced delivery of cintredekin besudotox in early-phase studies. Neurosurg Focus 20(4):E15PubMed
go back to reference Li C, Hall WA, Jin N, Todhunter DA, Panoskaltsis-Mortari A, Vallera DA (2002) Targeting glioblastoma multiforme with an IL-13/diphtheria toxin fusion protein in vitro and in vivo in nude mice. Protein Eng 15(5):419–427CrossRefPubMed Li C, Hall WA, Jin N, Todhunter DA, Panoskaltsis-Mortari A, Vallera DA (2002) Targeting glioblastoma multiforme with an IL-13/diphtheria toxin fusion protein in vitro and in vivo in nude mice. Protein Eng 15(5):419–427CrossRefPubMed
go back to reference Parkin DM, Bray F, Ferlay J, Pisani P (2002) Global cancer statistics, 2002. CA Cancer J Clin 55(2):74–108CrossRef Parkin DM, Bray F, Ferlay J, Pisani P (2002) Global cancer statistics, 2002. CA Cancer J Clin 55(2):74–108CrossRef
go back to reference Shimamura T, Fujisawa T, Husain SR, Kioi M, Nakajima A, Puri RK (2008) Novel role of IL-13 in fibrosis induced by nonalcoholic steatohepatitis and its amelioration by IL-13R-directed cytotoxin in a rat model. J Immunol 181:4656–4665PubMed Shimamura T, Fujisawa T, Husain SR, Kioi M, Nakajima A, Puri RK (2008) Novel role of IL-13 in fibrosis induced by nonalcoholic steatohepatitis and its amelioration by IL-13R-directed cytotoxin in a rat model. J Immunol 181:4656–4665PubMed
go back to reference Vogelbaum MA, Sampson JH, Kunwar S, Chang SM, Shaffrey M, Asher AL, Lang FF, Croteau D, Parker K, Grahn AY, Sherman JW, Husain SR, Puri RK (2007) Convection-enhanced delivery of cintredekin besudotox (interleukin-13-PE38QQR) followed by radiation therapy with and without temozolomide in newly diagnosed malignant gliomas: phase I study of final safety results. Neurosurgery 61(5):1031–1038CrossRefPubMed Vogelbaum MA, Sampson JH, Kunwar S, Chang SM, Shaffrey M, Asher AL, Lang FF, Croteau D, Parker K, Grahn AY, Sherman JW, Husain SR, Puri RK (2007) Convection-enhanced delivery of cintredekin besudotox (interleukin-13-PE38QQR) followed by radiation therapy with and without temozolomide in newly diagnosed malignant gliomas: phase I study of final safety results. Neurosurgery 61(5):1031–1038CrossRefPubMed
Metadata
Title
Expression of IL-13Rα2 in liver cancer cells and its effect on targeted therapy of liver cancer
Authors
Lingling Hou
Juan Du
Jianwei Wang
Yanfeng Liu
Weimin Sun
Yanpeng Zheng
Lishu Zhang
Honggang Hu
Xinxian Dai
Weijun Guan
Yuehui Ma
Tao Hong
Publication date
01-06-2010
Publisher
Springer-Verlag
Published in
Journal of Cancer Research and Clinical Oncology / Issue 6/2010
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-009-0724-z

Other articles of this Issue 6/2010

Journal of Cancer Research and Clinical Oncology 6/2010 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine