Natural killer cells inhibit breast cancer cell invasion through downregulation of urokinasetype plasminogen activator.
Oncol Rep
; 45(1): 299-308, 2021 01.
Article
em En
| MEDLINE
| ID: mdl-33155661
ABSTRACT
Triplenegative breast cancer (TNBC) is one of the most aggressive types of breast cancer, and there is no effective therapeutic target to date. Natural killer (NK) cells are functionally diverse lymphocytes that recognize and kill cancer cells. Although it is clear that NK cells exert antitumor activity in the tumor microenvironment, their role in the aggressive progression of TNBC has not been elucidated in detail. In the present study, we investigated the effect of NK cells on MDAMB231 TNBC cells using an indirect coculture system. The invasive phenotype of MDAMB231 cells was significantly inhibited by coculture with NK cells. Notably, the expression of urokinasetype plasminogen activator (uPA) was markedly reduced by NK cells. Cytokine array analysis showed that the levels of interleukin (IL)10, IL6, IL8, CC motif ligand (CCL)5, and CCL2 were increased in conditioned media from the cocultured cells. Among these cytokines, IL6 played a crucial role in the NK cellinduced uPA downregulation and inhibition of the invasive phenotype of MDAMB231 cells and Hs578T cells. We analyzed the Gene Expression Profiling Interactive Analysis database for correlations between IL6 and uPA with the overall survival of breast cancer patients. The KaplanMeier survival analysis revealed that a low IL6/uPA ratio was associated with the poor survival of breast cancer patients, suggesting it as an important factor for determining the overall survival of breast cancer patients. Taken together, our findings demonstrate that NK cells in the tumor microenvironment inhibit the invasiveness of TNBC cells through the IL6mediated inhibition of uPA.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Células Matadoras Naturais
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Ativador de Plasminogênio Tipo Uroquinase
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Regulação Neoplásica da Expressão Gênica
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article