title: Intranasal Administration of Type V Collagen Reduces Lung Carcinogenesis through Increasing Endothelial and Epithelial Apoptosis in a Urethane-Induced Lung Tumor Model.
abstract: Type V collagen (Col V) is a "minor" component of normal lung extracellular matrix, which is subjected to decreased and abnormal synthesis in human lung infiltrating adenocarcinoma. We previously reported that a direct link between low amounts of Col V and decreased cell apoptosis may favor cancer cell growth in the mouse lung after chemical carcinogenesis. Moreover, this collagen species was able to trigger DNA fragmentation and impair survival of neoplastic cells. In this study, we have extended our investigation with the aim to obtain further evidence that the death induced by Col V-treatment is of the caspase-9 apoptotic type. We used (1) optical and electron microscopy, (2) quantitation of TUNEL-labeled cells and (3) analysis of the expression levels of Col V and selected genes coding for apoptosis-linked factors, by conventional RT-PCR. BALB/c mice were injected intraperitoneally with 1.5 g/kg body weight of urethane. After urethane injection, the animals received intranasal administration of 20 µg/20 µl of Col V every day during 2 months. We report here that Col V treatment was able to determine significant increase in Col V protein and gene expression and in the percentage of TUNEL-positive cells, to up-regulate caspase-9, resulting in low growth of tumor cells. Our data validate chemical carcinogenesis as a suitable "in vivo" model for further and more detailed studies on the molecular mechanisms of the death response induced by Col V in lung infiltrating adenocarcinoma opening new strategies for treatment.
authors.affiliation: Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo 455, sala 1143, São Paulo, SP, CEP 01296-903, Brazil.
authors.forename: Edwin Roger
authors.initials: ER
authors.lastname: Parra
authors.affiliation: Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo 455, sala 1143, São Paulo, SP, CEP 01296-903, Brazil.
authors.forename: Renata Antunes
authors.initials: RA
authors.lastname: Alveno
authors.affiliation: Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo 455, sala 1143, São Paulo, SP, CEP 01296-903, Brazil.
authors.forename: Carolina Brito
authors.initials: CB
authors.lastname: Faustino
authors.affiliation: Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo 455, sala 1143, São Paulo, SP, CEP 01296-903, Brazil.
authors.forename: Paula Yume Sato Serzedello
authors.initials: PY
authors.lastname: Corrêa
authors.affiliation: Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo 455, sala 1143, São Paulo, SP, CEP 01296-903, Brazil.
authors.forename: Camilla Mutai
authors.initials: CM
authors.lastname: Vargas
authors.affiliation: Discipline of Rheumatology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Jymenez
authors.initials: J
authors.lastname: de Morais
authors.affiliation: Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo 455, sala 1143, São Paulo, SP, CEP 01296-903, Brazil.
authors.forename: Maristela Peres
authors.initials: MP
authors.lastname: Rangel
authors.affiliation: Discipline of Rheumatology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Ana Paula Pereira
authors.initials: AP
authors.lastname: Velosa
authors.affiliation: Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo 455, sala 1143, São Paulo, SP, CEP 01296-903, Brazil.
authors.forename: Alexandre Todorovic
authors.initials: AT
authors.lastname: Fabro
authors.affiliation: Discipline of Rheumatology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Walcy Rosolia
authors.initials: WR
authors.lastname: Teodoro
authors.affiliation: Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo 455, sala 1143, São Paulo, SP, CEP 01296-903, Brazil. vcapelozzi@lim05.fm.usp.br.
authors.forename: Vera Luiza
authors.initials: VL
authors.lastname: Capelozzi
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D017209:Apoptosis; D063646:Carcinogenesis; D024062:Collagen Type V / Q000008:administration & dosage* / Q000276:immunology; D053938:DNA Fragmentation; D042783:Endothelial Cells / Q000166:cytology*; D004847:Epithelial Cells / Q000166:cytology*; D004848:Epithelium / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D014520:Urethane / Q000009:adverse effects
chemical_list: D024062:Collagen Type V; D014520:Urethane
keywords: Apoptosis; Chemically-induced lung carcinogenesis; Immune response; Molecular biology; Type V collagen; Vascular endothelial growth factor