Pituitary sex hormones enhance the prometastatic potential of human lung cancer cells by downregulating the intracellular expression of heme oxygenase1.
Int J Oncol
; 50(1): 317-328, 2017 Jan.
Article
em En
| MEDLINE
| ID: mdl-27922667
ABSTRACT
We report that human lung cancer cell lines express functional receptors for pituitary sex hormones (SexHs) and respond to stimulation by folliclestimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL). Expression of these receptors has also been confirmed in patient lung cancer samples at the mRNA level. Stimulation of human lung cancer cell lines with FSH, LH, or PRL stimulated migration and chemotaxis, and some cell lines responded by enhanced proliferation. Moreover, priming of human lung cancer cells by exposing them to pituitary SexHs resulted in enhanced seeding efficiency of injected human lung cancer cells into bone marrow, liver, and lungs in an immunodeficient mouse model. The chemotaxis of lung cancer cell lines corresponded with the activity of heme oxygenase1 (HO1), as stimulation of these cells by FSH, LH, and PRL downregulated its expression in a p38 MAPKdependent manner. Moreover, while downregulation of HO1 by the smallmolecule inhibitor tin protoporphyrin (SnPP) promoted migration, upregulation of HO1 by the smallmolecule activator cobalt protoporphyrin (CoPP) showed the opposite effect. Based on this finding, we propose that pituitary SexHs play a significant role in the pathogenesis of lung cancer, particularly when the blood level of FSH increases due to gonadal dysfunction with advanced age. Finally, we propose that upregulation of HO1 expression by a smallmolecule activator may be effective in controlling SexHinduced cell migration in lung cancer.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Quimiotaxia
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Proliferação de Células
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Heme Oxigenase-1
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Neoplasias Pulmonares
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article