Matrix metalloproteinase 12 promotes tumor propagation in the lung.
J Thorac Cardiovasc Surg
; 155(5): 2164-2175.e1, 2018 05.
Article
em En
| MEDLINE
| ID: mdl-29429629
ABSTRACT
OBJECTIVE:
Past studies are inconsistent with regard to the role of matrix metalloproteinase 12 in lung tumorigenesis. This is due, in part, to differential tumorigenesis based on tumor-derived versus immune-derived matrix metalloproteinase 12 expression. Our study aims to thoroughly dissect the role of matrix metalloproteinase 12 in lung tumorigenesis.METHODS:
We tested matrix metalloproteinase 12 expression and the association with prognosis using a tissue array and a published non-small cell lung cancer gene expression database. In addition, we characterized the contribution of matrix metalloproteinase 12 to tumor propagation in the lung using a series of in vitro and in vivo studies.RESULTS:
Tumor cells of a diverse set of human lung cancers stained positive for matrix metalloproteinase 12, and high matrix metalloproteinase 12 mRNA levels in the tumor were associated with reduced survival. The lung microenvironment stimulated endogenous production of matrix metalloproteinase 12 in lung cancer cells (human 460 lung cancer cell line, Lewis lung carcinoma). In vitro, matrix metalloproteinase 12 knockout Lewis lung carcinoma and Lewis lung carcinoma cells had the same proliferation rate, but Lewis lung carcinoma showed increased invasiveness. In vivo, deficiency of matrix metalloproteinase 12 in Lewis lung carcinoma cells, but not in the host, reduced tumor growth and invasiveness.CONCLUSIONS:
We suggest that tumor cell-derived matrix metalloproteinase 12 promotes tumor propagation in the lung and that in the context of pulmonary malignancies matrix metalloproteinase 12 should further be tested as a potential novel therapeutic target.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Biomarcadores Tumorais
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Movimento Celular
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Carcinoma Pulmonar de Células não Pequenas
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Carcinoma Pulmonar de Lewis
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Metaloproteinase 12 da Matriz
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Neoplasias Pulmonares
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
J Thorac Cardiovasc Surg
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Israel