Anti-EGFR Antibody Reduces Lung Nodules by Inhibition of EGFR-Pathway in a Model of Lymphangioleiomyomatosis.

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 sclero...

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Publicado en:BioMed Research International Vol. 2015; pp. 1 - 15
Autores principales: Lesma, Elena, Chiaramonte, Eloisa, Ancona, Silvia, Orpianesi, Emanuela, Di Giulio, Anna Maria, Gorio, Alfredo
Formato: pictorial research tables/charts Journal Article
Publicado: Wiley-Blackwell 1/28/2015
Acceso en línea:Ver este registro en EBSCOhost
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      dt: 1/28/2015
      vid: 2015
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      pub: Wiley-Blackwell
      place: Malden, Massachusetts
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        10.1155/2015/315240
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        atl: Anti-EGFR Antibody Reduces Lung Nodules by Inhibition of EGFR-Pathway in a Model of Lymphangioleiomyomatosis.
      aug:
        au:
          Lesma, Elena
          Chiaramonte, Eloisa
          Ancona, Silvia
          Orpianesi, Emanuela
          Di Giulio, Anna Maria
          Gorio, Alfredo
        affil: Laboratories of Pharmacology, Department of Health Sciences, University of Milano, Via di Rudini’ 8, 20142 Milano, Italy
      sug:
        subj:
          Lymphangioma
          Protein-Tyrosine Kinases
          Epidermal Growth Factors
          Histology Methods
          Animal Studies
          In Vivo Studies
          Blotting, Western
          One-Way Analysis of Variance
          Immunohistochemistry
          Mice
          Cell Culture Techniques
          T-Tests
          Funding Source
      ab: 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.
      pubtype: Academic Journal
      doctype:
        pictorial
        research
        tables/charts
        Journal Article
      ougenre: Article
    language: English
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