Intranasal Administration of Type V Collagen Reduces Lung Carcinogenesis through Increasing Endothelial and Epithelial Apoptosis in a Urethane-Induced Lung Tumor Model

Author(s):Show less -

Parra, Edwin Roger ^[1] ; Alveno, Renata Antunes ^[1] ; Faustino, Carolina Brito ^[1] ; Sato Serzedello Correa, Paula Yume ^[1] ; Vargas, Camilla Mutai ^[1] ; de Morais, Jymenez ^[2] ; Rangel, Maristela Peres ^[1] ; Pereira Velosa, Ana Paula ^[2] ; Fabro, Alexandre Todorovic ^[1] ; Teodoro, Walcy Rosolia ^[2] ; Capelozzi, Vera Luiza ^[1]

Affiliation

^[1] Univ Sao Paulo, Dept Patol, Fac Med, Ave Dr Arnaldo 455, Sala 1143, BR-01296903 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Discipline Rheumatol, Fac Med, Sao Paulo - Brazil

• Document type: Journal article
• Source: ARCHIVUM IMMUNOLOGIAE ET THERAPIAE EXPERIMENTALIS; v. 64, n. 4, p. 321-329, AUG 2016.
• Web of Science Citations: 1

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 A mu g/20 A mu l 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. (AU)