RESUMEN
BACKGROUND: Treatments based on the inhibition of pivotal signals of cancer stem cells (CSCs) are on a promising track. Recent studies have shown that targeting CSCs with broader immune-based therapeutic methods, for example, the anti-CD47 treatment, may serve as a more potent strategy for eliminating these intractable cells. We aimed to explore the prognostic effects of CD47/CD133 and the potential therapeutic significance of CD47 in esophageal squamous cell carcinoma (ESCC). METHODS: Immunohistochemistry was employed to identify the characteristics of CD47 and CD133 in 26 pairs of tumor tissues and adjacent non-tumor tissues and 136 ESCC tissues. Kaplan-Meier analysis and Cox proportional hazards models were built for estimating the prognostic values of CD47 and CD133 expression and their combined stemness index. Sphere formation assays were undertaken to explore the effects of CD47 inhibition on primary human ESCC CSCs. RESULTS: Results conclude that CD47 and CD133 expression is increased in tumor tissues as compared to adjacent non-tumor tissues. A positive correlation between CD47/CD133 expression and differentiation was found in 136 ESCC patients. Survival analysis indicated that patients with high CD47 or CD133 expression exhibited poor overall survival and progression-free survival (PFS). The combination of high CD47 and CD133 expression was a reliable independent prognostic factor for both OS (HR = 1.940, 95% CI = 1.399-2.690, P < 0.0001) and progression-free survival (HR = 1.883, 95% CI = 1.384-2.562, P < 0.0001). Notably, CD47+ CD133+ ESCC cells were observed to possess the characteristics of CSCs, and anti-CD47 treatment veritably eliminated the CSCs pool. CONCLUSIONS: The stemness index determined by the expression of CD47 and CD133 is a promising prognostic predictor, and CD47 is a potential therapeutic target for CSCs in ESCC patients.
Asunto(s)
Antígeno AC133/metabolismo , Antígeno CD47/metabolismo , Carcinoma de Células Escamosas de Esófago/metabolismo , Carcinoma de Células Escamosas de Esófago/mortalidad , Células Madre Neoplásicas/metabolismo , Antígeno AC133/genética , Adulto , Anciano , Biomarcadores de Tumor , Antígeno CD47/genética , Carcinoma de Células Escamosas de Esófago/diagnóstico , Carcinoma de Células Escamosas de Esófago/terapia , Femenino , Expresión Génica , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Análisis de SupervivenciaRESUMEN
The authors' previous study demonstrated that Golgi phosphoprotein 3 (GOLPH3) was significantly overexpressed in esophageal squamous cell carcinoma (ESCC), correlating with poor patient survival. In the present study, GOLPH3 stable overexpression and knockdown KYSE140 cell lines were constructed. Cell proliferation, colony formation, cell cycle progression and tumorigenesis assays were performed. The results revealed that GOLPH3 promoted ESCC cell growth and proliferation. The effects of GOLPH3 on the mechanistic target of rapamycin (mTOR) and Wnt/ßcatenin signaling pathways were investigated using western blot analyis and dualluciferase reporter assays, and were observed to be activated in cells with GOLPH3 overexpression. Furthermore, overexpression of GOLPH3 resulted in the downregulation of p21 protein, upregulation of cyclin D1 and increased retinoblastomaassociated protein phosphorylation, consequently leading to accelerated cell cycle progression. In addition, GOLPH3 knockdown resulted in reversed effects. The results of the current study suggest that GOLPH3 serves an important role in promoting tumorigenicity of ESCC via mTOR and Wnt/ßcatenin signaling pathway activation.
Asunto(s)
Proteínas de la Membrana/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Proteínas Wnt/metabolismo , Vía de Señalización Wnt , beta Catenina/metabolismo , Animales , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Puntos de Control del Ciclo Celular , Línea Celular Tumoral , Proliferación Celular , Transformación Celular Neoplásica , Ciclina D1/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Regulación hacia Abajo , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago , Femenino , Humanos , Proteínas de la Membrana/antagonistas & inhibidores , Proteínas de la Membrana/genética , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Interferencia de ARN , Regulación hacia ArribaRESUMEN
The purpose of this study was to realize the security of safe wintering of winter rapeseed in dry and cold regions of northern China. Experiments were conducted with 18 winter rapeseed (Brassica campestris) varieties at 57 sites from 2008 to 2013 to statistically analyze the wintering rate variation of different varieties in dry and cold regions of northern China. The results showed that, the wintering rate varied from 70% to 90% during the study period in different regions, which had no significant difference between different years and varieties, and had high stability and remarkable economic benefit. With Tianshui as a starting point of winter rapeseed planting, the wintering-safe regions included all Gansu Province , the south of Lasa and Linzhi of Xizang, the east of Minhe of Qinghai, up to Urumqi and Baicheng, and the south of Aletai, Tacheng, the east of Kashi of Xinjiang, it also included the regions along Yellow River eastward to Ningxia, the south of Linhe of Inner Mongolia, the north of Shaanxi, the vicinage of Qixian in Shanxi, Daming in Hebei, Tianjin, Beijing, the north of Weifang of Shandong, the south of Huludao of Liaoning and Yanbian of Jilin. Longyou 6, Longyou 7, Longyou 8 and Longyou 9 were the wintering-safe B. rapa varieties.