ECE2015 Guided Posters Endocrine tumours and neoplasia – NETS (9 abstracts)
Receptor tyrosine kinase expression and their role in the response to target therapy in bronchopulmonary NET
Tersa Gagliano , Katiusci Benfini , Erica Gentilin , Simona Falletta , Marta Bondanelli , Carmelina Di Pasquale , Eleonora Riva , Ettore degli Ubertu & Maria Chiara Zatelli
Section of Endocrinology and Internal Medicine, Department of Medical Science, University of Ferrara, Ferrara, Italy.
Surgery is not feasible for infiltrating and metastatic bronchopulmonary NET (BP-NET). In those cases, medical therapy is tried with controversial results. Thus, it is important to identify new therapeutic targets to provide adequate medical treatment for patients with BP-NET. Sunitinib, is a multi-targeted receptor tyrosine kinase inhibitor (TKI), mainly described to inhibit VEGFR.
The aim of our study is to verify whether insulin receptor (IR), IGF1R, and EGFR could be involved in Sunitinib mechanism of action in BP-NET cells.
For this purpose human BP-NET cell lines and human BP-NET primary cultures were treated with Sunitinib and/or EGF, IGF1, or VEGF. Cell viability and caspase 3/7 activation were measured after 48 h of treatment. Receptor expression was detected by Western blot in both cell lines and primary cultures. Phosphorylation of IGF1R and EGFR was analysed by Alphascreen sure fire assay.
Our results show that Sunitinib is capable of inhibiting cell viability of BP-NET cell lines and primary cultures, and activates caspase 3/7. Both events are counteracted by EGF and IGF1, but not by VEGF. Moreover, both cell lines and tissues invariably express IR, IGF1, and EGFR, while VEGFRs are expressed only in some samples. Treatment with Sunitinib decreased the phosphorylation of both EGFR and IGFR1, in both cell lines and primary cultures.
In conclusion, these data indicate that the expression of EGFR and IGF1R are important for Sunitinib action in BP-NET. The effects of Sunitinib on BP-NET cell viability could be due to a double inhibition of EGFR and IGF1R, while the role of IR needs to be further investigated.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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