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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Chronic exposure of lung alveolar epithelial type II cells to tobacco-specific carcinogen NNK results in malignant transformation: A new in vitro lung carcinogenesis model

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Autor(es):
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Mennecier, Gregory [1] ; Torres, Luciana N. [1] ; Cogliati, Bruno [1] ; Sanches, Daniel S. [1] ; Mori, Claudia M. [1] ; Latorre, Andreia O. [1] ; Chaible, Lucas M. [1] ; Mackowiak, Ivone I. [1] ; Nagamine, Marcia K. [1] ; Da Silva, Tereza C. [1] ; Fukumasu, Heidge [2] ; Zaidan Dagli, Maria Lucia [1]
Número total de Autores: 12
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Dept Pathol, Sch Vet Med & Anim Sci, BR-05508900 Sao Paulo - Brazil
[2] Univ Sao Paulo, Dept Anim Sci, Sch Anim Sci & Food Engn, Pirassununga, SP - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: Molecular Carcinogenesis; v. 53, n. 5, p. 392-402, MAY 2014.
Citações Web of Science: 7
Resumo

Lung cancer is the leading cause of cancer-related mortality in both men and women throughout the world. This disease is strongly associated with tobacco smoking. The aim of this manuscript was to establish an in vitro model that mimics the chronic exposures of alveolar epithelial type II cells to the tobacco-specific nitrosamine carcinogen, NNK. Immortalized non-neoplastic alveolar epithelial cells type II, (E10 cells), from BALB/c mice were exposed to low concentration of NNK (100 pM) during 5, 10, 15, and 20 cycles of 48 h. NNK-transformed cells showed an increase of proliferation rate and motility. Moreover, these cells underwent epithelial-to-mesenchymal transition (EMT). Increased migratory capacity and EMT were correlated to the time of exposure to NNK. NNK-transformed cells were tested for their growth and metastatic capacity in vivo. Subcutaneous injection of cells exposed to NNK for 20 cycles (E10-NNK20 clone) into BALB/c mice led to the formation of subcutaneous tumors that arose after 40 +/- 17 d in all animals, which died 95 +/- 18 d after cell inoculation, with lymph nodes and lung metastasis. The morphological characteristics of tumors were compatible with metastatic undifferentiated carcinoma. Cells exposed to NNK for 5-10 cycles did not display metastatic capacity, while those exposed for 15 cycles displayed low capacity. Our results show that prolonged exposures to NNK led the cells to increasingly acquire malignant properties. The cellular model presented in this study is suitable for studying the molecular events involved in the different stages of malignant transformation. (c) 2012 Wiley Periodicals, Inc. (AU)

Processo FAPESP: 09/52106-1 - Carcinogênese mamária e pulmonar in vitro: estudo da proliferação celular, apoptose, capacidade de comunicação por junções do tipo gap e expressão de conexinas durante o processo
Beneficiário:Gregory Mennecier
Linha de fomento: Bolsas no Brasil - Pós-Doutorado