title: Caveolin 1 expression favors tumor growth and is associated with poor survival in primary lung adenocarcinomas.
abstract: Despite the consolidated clinico-pathological correlates of Caveolin 1 expression in non-small cell lung cancer, the available data on the role of Caveolin 1 in relation to proliferation, migration, and metastasis in lung adenocarcinoma cells is still scant. Here, we aimed to confirm whether Caveolin 1 may act as a promoter of cell growth in human lung adenocarcinoma using in vitro and in vivo models, supported by a survival analysis of Caveolin 1 expression in a series of 116 primary lung adenocarcinomas. The silencing of endogenous Caveolin 1 expression in H522 lung adenocarcinoma cells through stable shRNA transfection significantly inhibited cellular proliferation in vitro and in vivo, in a lung adenocarcinoma xenograft mouse model. The bioluminescence imaging analysis revealed that tumors derived from Caveolin 1 shRNA-transfected cells grew slower than control xenografts. However, this difference progressively diminished over time and was definitively lost after 21 days. This was consistent with a progressive Caveolin 1 re-expression, which started at day 7. The association between the restored expression of Caveolin 1 and the restart of tumor growth in vivo supports the booster role of Caveolin 1 in lung adenocarcinoma progression. To further confirm this role, Caveolin 1 expression was assessed by immunohistochemistry in a series of 116 human lung adenocarcinomas. Positive Caveolin 1 tumors accounted for 20% of cases and were associated with a significantly worse overall survival compared to Caveolin 1-negative cancers. Taken together, these data highlight that Caveolin 1 expression confers a proliferative advantage in lung adenocarcinoma cells, thus fostering increased tumor aggressiveness.
authors.affiliation: 1 Department of Oncology, University of Turin, Orbassano, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Duregon
authors.affiliation: 2 Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Senetta
authors.affiliation: 2 Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Bertero
authors.affiliation: 3 Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Bussolati
authors.affiliation: 2 Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Annaratone
authors.affiliation: 2 Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pittaro
authors.affiliation: 1 Department of Oncology, University of Turin, Orbassano, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Papotti
authors.affiliation: 2 Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Marchiò
authors.affiliation: 2 Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Cassoni
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000818:Animals; D051242:Caveolin 1 / Q000096:biosynthesis* / Q000235:genetics; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D014162:Transfection
chemical_list: D051242:Caveolin 1; D034741:RNA, Small Interfering
keywords: Caveolin 1; lung adenocarcinoma; prognosis; proliferation