Anti-EGFR Antibody Reduces Lung Nodules by Inhibition of EGFR-Pathway in a Model of LymphangioleiomyomatosisReportar como inadecuado

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BioMed Research International - Volume 2015 2015, Article ID 315240, 14 pages -

Research ArticleLaboratories of Pharmacology, Department of Health Sciences, University of Milano, Via di Rudini’ 8, 20142 Milano, Italy

Received 6 August 2014; Accepted 26 November 2014

Academic Editor: Vasiliki Galani

Copyright © 2015 Elena Lesma et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


EGFR belongs to the HER-ErbB 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 whose proliferation depends on EGF and monoclonal anti-EGFR antibodies reduced proliferation and caused cell death. We demonstrated that the dependency 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 has a potential in treatment of LAM-TSC lung alterations.

Autor: Elena Lesma, Eloisa Chiaramonte, Silvia Ancona, Emanuela Orpianesi, Anna Maria Di Giulio, and Alfredo Gorio



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