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

Archivum Immunologiae et Therapiae Experimentalis volume 64, pages 321–329 (2016)Cite this article

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.

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Acknowledgments

This study was supported by the following Brazilian agencies: Foundation for the Support of Research of the State of São Paulo (FAPESP, 08/58743-0, 08/58742-4 and 08/58741-8 process) and National Council for Scientific and Technological Development (CNPq).

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Affiliations

  1. Departamento de Patologia, Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo 455, sala 1143, São Paulo, SP, CEP 01296-903, Brazil

    Edwin Roger Parra, Renata Antunes Alveno, Carolina Brito Faustino, Paula Yume Sato Serzedello Corrêa, Camilla Mutai Vargas, Maristela Peres Rangel, Alexandre Todorovic Fabro & Vera Luiza Capelozzi

  2. Discipline of Rheumatology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

    Jymenez de Morais, Ana Paula Pereira Velosa & Walcy Rosolia Teodoro

Authors
  1. Edwin Roger Parra
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  2. Renata Antunes Alveno
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  3. Carolina Brito Faustino
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  4. Paula Yume Sato Serzedello Corrêa
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  5. Camilla Mutai Vargas
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  6. Jymenez de Morais
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  7. Maristela Peres Rangel
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  8. Ana Paula Pereira Velosa
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  9. Alexandre Todorovic Fabro
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  10. Walcy Rosolia Teodoro
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  11. Vera Luiza Capelozzi
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Correspondence to Vera Luiza Capelozzi.

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Parra, E.R., Alveno, R.A., Faustino, C.B. et al. Intranasal Administration of Type V Collagen Reduces Lung Carcinogenesis through Increasing Endothelial and Epithelial Apoptosis in a Urethane-Induced Lung Tumor Model. Arch. Immunol. Ther. Exp. 64, 321–329 (2016). https://doi.org/10.1007/s00005-016-0390-1

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  • DOI: https://doi.org/10.1007/s00005-016-0390-1

Keywords

  • Chemically-induced lung carcinogenesis
  • Molecular biology
  • Apoptosis
  • Type V collagen
  • Immune response
  • Vascular endothelial growth factor