Suppression of activin A signals inhibits growth of malignant pleural mesothelioma cells

被引：25

作者：

Hoda, M. A. ^{[1
,2
]}

Munzker, J. ^{[1
]}

Ghanim, B. ^{[2
]}

Schelch, K. ^{[1
]}

Klikovits, T. ^{[2
]}

Laszlo, V. ^{[2
]}

Sahin, E. ^{[1
]}

Bedeir, A. ^{[1
]}

Lackner, A. ^{[1
]}

Dome, B. ^{[2
,3
]}

Setinek, U. ^{[4
]}

Filipits, M. ^{[1
]}

Eisenbauer, M. ^{[1
]}

Kenessey, I. ^{[5
]}

Torok, S. ^{[3
]}

Garay, T. ^{[5
]}

Hegedus, B. ^{[1
,2
,5
]}

Catania, A. ^{[6
]}

Taghavi, S. ^{[2
]}

Klepetko, W. ^{[2
]}

Berger, W. ^{[1
]}

Grusch, M. ^{[1
]}

机构：

[1] Med Univ Vienna, Dept Med 1, Inst Canc Res, Ctr Comprehens Canc, Borschkegasse 8A, A-1090 Vienna, Austria

[2] Med Univ Vienna, Div Thorac Surg, Dept Surg, Ctr Comprehens Canc, A-1090 Vienna, Austria

[3] Natl Koranyi Inst TB & Pulmonol, Budapest, Hungary

[4] Otto Wagner Hosp, Div Pathol, Vienna, Austria

[5] Semmelweis Univ, Dept Pathol 2, Budapest, Hungary

[6] Osped Policlin, Milan, Italy

来源：

BRITISH JOURNAL OF CANCER | 2012年 / 107卷 / 12期

关键词：

mesothelioma; activin; activin receptor; SMAD signalling; targeted therapy; FACTOR-BETA; CYCLE ARREST; EXPRESSION; PROLIFERATION; RECEPTORS; APOPTOSIS; PROGRESSION; ANTAGONIST; SURVIVAL; THERAPY;

D O I：

10.1038/bjc.2012.519

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BACKGROUND: Activins control the growth of several tumour types including thoracic malignancies. In the present study, we investigated their expression and function in malignant pleural mesothelioma (MPM). METHODS: The expression of activins and activin receptors was analysed by quantitative PCR in a panel of MPM cell lines. Activin A expression was further analysed by immunohistochemistry in MPM tissue specimens (N=53). Subsequently, MPM cells were treated with activin A, activin receptor inhibitors or activin-targeting siRNA and the impact on cell viability, proliferation, migration and signalling was assessed. RESULTS: Concomitant expression of activin subunits and receptors was found in all cell lines, and activin A was overexpressed in most cell lines compared with non-malignant mesothelial cells. Similarly, immunohistochemistry demonstrated intense staining of tumour cells for activin A in a subset of patients. Treatment with activin A induced SMAD2 phosphorylation and stimulated clonogenic growth of mesothelioma cells. In contrast, treatment with kinase inhibitors of activin receptors (SB-431542, A-8301) inhibited MPM cell viability, clonogenicity and migration. Silencing of activin A expression by siRNA oligonucleotides further confirmed these results and led to reduced cyclin D1/3 expression. CONCLUSION: Our study suggests that activin A contributes to the malignant phenotype of MPM cells via regulation of cyclin D and may represent a valuable candidate for therapeutic interference. British Journal of Cancer (2012) 107, 1978-1986. doi:10.1038/bjc.2012.519 www.bjcancer.com Published online 20 November 2012 (C) 2012 Cancer Research UK

引用

页码：1978 / 1986

页数：9

共 42 条

[1] Activin enhances skin tumourigenesis and malignant progression by inducing a pro-tumourigenic immune cell response [J].