RESUMEN
The inhibitor of growth 5 (ING5) is a new candidate tumor suppressor gene (TSG) of the ING family. So far, there have been many reports about its functions related to cancer development. However, the biological roles of ING5 in esophageal squamous cell carcinoma (ESCC) remain unclear. In the present study, we demonstrated that ING5 was lowly expressed in ESCC tissues and cell lines. Overexpression of ING5 inhibited ESCC cell proliferation and invasion in vitro as well as suppressed tumor growth and metastasis in vivo. We also found that overexpression of ING5 significantly decreased the levels of p-AKT, NF-κB and MMP-9 in ECA109â¯cells. Taken together, these findings demonstrated that ING5 inhibited cell proliferation and invasion in ESCC through regulation of the Akt/NF-κB/MMP-9 signaling pathway. Thus, ING5 might be considered a promising target for ESCC treatment.
Asunto(s)
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/genética , Metaloproteinasa 9 de la Matriz/genética , FN-kappa B/genética , Proteínas Proto-Oncogénicas c-akt/genética , Factores de Transcripción/genética , Proteínas Supresoras de Tumor/genética , Animales , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Proliferación Celular , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago , Femenino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Metaloproteinasa 9 de la Matriz/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , FN-kappa B/metabolismo , Invasividad Neoplásica , Trasplante de Neoplasias , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Factores de Transcripción/metabolismo , Proteínas Supresoras de Tumor/metabolismoRESUMEN
Stepwise progression from adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) to lepidic predominant adenocarcinoma (LPA) was proposed by various scholars. Interstitial tumor-associated macrophages (TAMs) and various potential chemokines involved in the progression from AIS/MIA to LPA were hypothesized. In the present study, immunohistochemistry or immunofluorescent double staining was used to detect the expression of the TAMs marker cluster of differentiation (CD) 68, tumor-derived colony-stimulating factor (CSF)-1, interleukin (IL)-6, matrix metalloproteinase (MMP)-2, E-cadherin and Snail in lung adenocarcinoma specimens, including AIS/MIA, LPA and other types. It was observed that infiltrating TAMs were negatively associated with the prognosis of patients, and that the infiltration degree of interstitial TAMs was higher in LPA than that in AIS/MIA. In addition, E-cadherin, Snail and MMP-2 expression were significantly correlated with the infiltration degree of TAMs. Survival analysis revealed that co-expression of CD68, CSF-1 and IL-6 was an independent prognostic factor. Stratified analysis demonstrated that, in AIS/MIA patients, there was a statistically significant difference between the number of TAMs (TAMs ≤25 and TAMs >25) in the CD68+CSF-1+IL-6+ group compared with other groups (including CD68+CSF-1-IL-6-, CD68+CSF-1+IL-6-, CD68+CSF-1-IL-6+ and CD68- groups). By contrast, in patients with TAMs >25 and in patients with positive CD68, CSF-1 and IL-6 expression, the survival rates were not significantly different between AIS/MIA and LPA. These results suggested that co-expression of TAMs marker CD68, CSF-1 and IL-6 may be a valuable independent prognostic predictor in lung adenocarcinoma. TAMs may facilitate AIS/MIA progression to LPA, which may be closely associated with the induction of the epithelial-mesenchymal transition.