Tuberous Sclerosis Complex (TSC) is characterized by the multiorgan development of benign tumors and is related to lymphangioleiomyomatosis (LAM), a rare disease caused by abnormal growth of smooth muscle (ASM) cells within lung parenchyma and axial lymphatics. From an angiomyolipoma of a TSC2 patient and from chylous of a TSC-associated LAM patient, TSC2-/- ASM and LAM/TSC cells, respectively, have been isolated. Proliferation depends on epidermal growth factor (EGF) and antibodies to EGF receptor (anti-EGFR) caused cell death. We developed animal models by endonasal administration of TSC2-/- ASM or LAM/TSC cells in immunodeficient female athymic nude mice. Both cells were infiltrated into pulmonary alveolar walls where they caused enlarged alveolar spaces. Only LAM/TSC cell administration was associated to nodules development in lung parenchyma in 30 weeks. Pulmonary nodules arose in 46% of LAM/TSC cell administrated mice. This percentage significantly decreased after anti-EGFR (25%) or rapamycin (33%) treatments. Pulmonary nodules were localized near lymphatic and blood vessels or bronchioli and showed positivity to phospho-S6, and estrogen and progesterone receptors. Within the nodules we identified human LAM/TSC cells. In conclusion, LAM/TSC cells, but not TSC2-/- ASM cells, caused pulmonary nodule formation. Rapamycin and more significantly anti-EGFR antibody reduced the number of pulmonary metastases.

LAM/TSC cells cause pulmonary nodule development by endonasal administration in nude mice / E. Chiaramonte, C. Bernardelli, S. Ancona, E. Orpianesi, E. Lesma, A.M. Di Giulio, A. Gorio. ((Intervento presentato al convegno International TSC Congress tenutosi a Napoli nel 2012.

LAM/TSC cells cause pulmonary nodule development by endonasal administration in nude mice

C. Bernardelli;S. Ancona;E. Orpianesi;E. Lesma;A.M. Di Giulio;A. Gorio
2012-09

Abstract

Tuberous Sclerosis Complex (TSC) is characterized by the multiorgan development of benign tumors and is related to lymphangioleiomyomatosis (LAM), a rare disease caused by abnormal growth of smooth muscle (ASM) cells within lung parenchyma and axial lymphatics. From an angiomyolipoma of a TSC2 patient and from chylous of a TSC-associated LAM patient, TSC2-/- ASM and LAM/TSC cells, respectively, have been isolated. Proliferation depends on epidermal growth factor (EGF) and antibodies to EGF receptor (anti-EGFR) caused cell death. We developed animal models by endonasal administration of TSC2-/- ASM or LAM/TSC cells in immunodeficient female athymic nude mice. Both cells were infiltrated into pulmonary alveolar walls where they caused enlarged alveolar spaces. Only LAM/TSC cell administration was associated to nodules development in lung parenchyma in 30 weeks. Pulmonary nodules arose in 46% of LAM/TSC cell administrated mice. This percentage significantly decreased after anti-EGFR (25%) or rapamycin (33%) treatments. Pulmonary nodules were localized near lymphatic and blood vessels or bronchioli and showed positivity to phospho-S6, and estrogen and progesterone receptors. Within the nodules we identified human LAM/TSC cells. In conclusion, LAM/TSC cells, but not TSC2-/- ASM cells, caused pulmonary nodule formation. Rapamycin and more significantly anti-EGFR antibody reduced the number of pulmonary metastases.
Settore BIO/14 - Farmacologia
Associazione Sclerosi Tuberosa
LAM/TSC cells cause pulmonary nodule development by endonasal administration in nude mice / E. Chiaramonte, C. Bernardelli, S. Ancona, E. Orpianesi, E. Lesma, A.M. Di Giulio, A. Gorio. ((Intervento presentato al convegno International TSC Congress tenutosi a Napoli nel 2012.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/205869
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