EGFR belongs to the HER/Erb family of tyrosine kinase receptors and its activation in cancer cells has been linked with increased proliferation, angiogenesis, and metastasis. Lymphangioleiomyomatosis (LAM) is a rare, low-grade neoplasm that occurs sporadically or in association with tuberous sclerosis complex (TSC), a genetic, multisystem disorder characterized by hamartomas in several organs. From chylous of a LAM/TSC patient, we previously isolated smooth muscle-like LAM/TSC cells which proliferation depends on EGF and monoclonal antibodies anti-EGFR reduced proliferation and caused cell death. We demonstrated that the dependence from EGF was caused by the absence of tuberin. To study the role of EGFR pathway in vivo, we developed a mouse model by administration of LAM/TSC cells to female nude mice. LAM/TSC cells caused pulmonary airspace enlargement and, after 30 weeks, nodule formation which express EGFR. Anti-EGFR antibody decreased the number and dimension of lung nodules likely for the inhibition of Erk and S6 signaling, reversed the pulmonary alterations and reduced lymphatic and blood vessels. Moreover, in pulmonary nodules anti-EGFR antibody reduced the positivity to estrogen and progesterone receptors which enhance survival of LAM cells and Snail expression. These results suggest that the inhibition of EGFR signalling have a potential in treatment of LAM/TSC lung alterations.

Anti-EGFR antibody reduces lung nodules by inhibition of EGFR-pathway in a model of lymphangioleiomyomatosis / E. Lesma, E. Chiaramonte, S. Ancona, E. Orpianesi, A.M. Di Giulio, A. Gorio. - In: BIOMED RESEARCH INTERNATIONAL. - ISSN 2314-6141. - (2015 Jan), pp. 315240.1-315240.14. [10.1155/2015/315240]

Anti-EGFR antibody reduces lung nodules by inhibition of EGFR-pathway in a model of lymphangioleiomyomatosis

E. Lesma
;
E. Chiaramonte
Secondo
;
S. Ancona;E. Orpianesi;A.M. Di Giulio
Penultimo
;
A. Gorio
Ultimo
2015-01

Abstract

EGFR belongs to the HER/Erb family of tyrosine kinase receptors and its activation in cancer cells has been linked with increased proliferation, angiogenesis, and metastasis. Lymphangioleiomyomatosis (LAM) is a rare, low-grade neoplasm that occurs sporadically or in association with tuberous sclerosis complex (TSC), a genetic, multisystem disorder characterized by hamartomas in several organs. From chylous of a LAM/TSC patient, we previously isolated smooth muscle-like LAM/TSC cells which proliferation depends on EGF and monoclonal antibodies anti-EGFR reduced proliferation and caused cell death. We demonstrated that the dependence from EGF was caused by the absence of tuberin. To study the role of EGFR pathway in vivo, we developed a mouse model by administration of LAM/TSC cells to female nude mice. LAM/TSC cells caused pulmonary airspace enlargement and, after 30 weeks, nodule formation which express EGFR. Anti-EGFR antibody decreased the number and dimension of lung nodules likely for the inhibition of Erk and S6 signaling, reversed the pulmonary alterations and reduced lymphatic and blood vessels. Moreover, in pulmonary nodules anti-EGFR antibody reduced the positivity to estrogen and progesterone receptors which enhance survival of LAM cells and Snail expression. These results suggest that the inhibition of EGFR signalling have a potential in treatment of LAM/TSC lung alterations.
lymphnagioleiomyomatosis; tuberous sclerosis complex; EGF
Settore BIO/14 - Farmacologia
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/269301
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