Clinical relevance of integrin alpha 4 in gastrointestinal stromal tumours

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http://hdl.handle.net/10138/234502

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Pulkka , O-P , Mpindi , J-P , Tynninen , O , Nilsson , B , Kallioniemi , O , Sihto , H & Joensuu , H 2018 , ' Clinical relevance of integrin alpha 4 in gastrointestinal stromal tumours ' , Journal of Cellular and Molecular Medicine , vol. 22 , no. 4 , pp. 2220-2230 . https://doi.org/10.1111/jcmm.13502

Title: Clinical relevance of integrin alpha 4 in gastrointestinal stromal tumours
Author: Pulkka, Olli-Pekka; Mpindi, John-Patrick; Tynninen, Olli; Nilsson, Bengt; Kallioniemi, Olli; Sihto, Harri; Joensuu, Heikki
Contributor: University of Helsinki, Clinicum
University of Helsinki, Olli-Pekka Kallioniemi / Principal Investigator
University of Helsinki, HUSLAB
University of Helsinki, Olli-Pekka Kallioniemi / Principal Investigator
University of Helsinki, Translational Cancer Biology (TCB) Research Programme
University of Helsinki, Clinicum
Date: 2018-04
Language: eng
Number of pages: 11
Belongs to series: Journal of Cellular and Molecular Medicine
ISSN: 1582-4934
URI: http://hdl.handle.net/10138/234502
Abstract: The molecular mechanisms for the dissemination and metastasis of gastrointestinal stromal tumours (GIST) are incompletely understood. The purpose of the study was to investigate the clinical relevance of integrin alpha 4 (ITGA4) expression in GIST. GIST transcriptomes were first compared with transcriptomes of other types of cancer and histologically normal gastrointestinal tract tissue in the MediSapiens in silico database. ITGA4 was identified as an unusually highly expressed gene in GIST. Therefore, the effects of ITGA4 knock-down and selective integrin alpha 4 beta 1 (VLA-4) inhibitors on tumour cell proliferation and invasion were investigated in three GIST cell lines. In addition, the prognostic role of ITGA4 expression in cancer cells was investigated in a series of 147 GIST patients with immunohistochemistry. Inhibition of ITGA4-related signalling decreased GIST cell invasion in all investigated GIST cell lines. ITGA4 protein was expressed in 62 (42.2%) of the 147 GISTs examined, and expression was significantly associated with distant metastases during the course of the disease and several adverse prognostic features. Patients whose GIST expressed strongly ITGA4 had unfavourable GIST-specific survival and overall survival compared to patients with low or no ITGA4 expression. Taken together, ITGA4 is an important integrin in the molecular pathogenesis of GIST and may influence their clinical behaviour.
Subject: gastrointestinal stromal tumour
ITGA4
survival
metastasis
proliferation
invasion
POOR-PROGNOSIS
CELL-GROWTH
SURVIVAL
RECURRENCE
IMATINIB
CANCER
VLA-4
RISK
KIT
INACTIVATION
3122 Cancers
3111 Biomedicine
1182 Biochemistry, cell and molecular biology
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