RESUMEN
BACKGROUND: Cancer-associated fibroblasts (CAFs), one of the main members of stromal cells in tumor microenvironment are proposed to play a central role in promoting tumor metastasis. It is unclear whether and how CAFs mediates tumor metastasis or chemoresistance in human ovarian cancer. METHODS: CAFs were extracted from human ovarian cancer tissues (OCs) of patients with different kinds of histological types. RESULTS: We found that CAFs showed more aggressive potency than those tumor cells, both of which were isolated from the same ovarian cancer specimen. Moreover, when co-cultured with CAFs, cell migration abilities of ovarian cancer cells (SKOV3, OVCAR3 and HEY) were significantly increased. Next, we preliminarily detected a higher CAFs density in sections of metastatic lesions than those in primary tumor site of primary OCs clinically. However, no significant difference of stromal derived factors-1α (SDF-1α) production from CAFs was found between primary and metastatic lesions. Additionally, in contrast with tumor cells, CAFs exhibited obvious apoptosis resistance when treated with cisplatin. Furthermore, we found that cisplatin-induced cytotoxicity and apoptosis were significantly inhibited by co-cultured with recombinant human SDF-1α in SKOV3 in a time and dose-dependent manner, and this effect was suppressed by the CXCR4 antagonist AMD3100. CONCLUSIONS: CAFs might be involved in the malignant metastasis in human ovarian cancer through promoting cell migration in tumor cells. And their resistance to cytotoxic agents might be mediated by paracrine SDF-1α/CXCR4 signaling in ovarian cancer.
Asunto(s)
Fibroblastos Asociados al Cáncer , Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Fibroblastos Asociados al Cáncer/patología , Quimiocina CXCL12 , Cisplatino/farmacología , Apoptosis , Línea Celular Tumoral , Movimiento Celular , Fibroblastos , Proliferación Celular , Microambiente TumoralRESUMEN
PURPOSE: To determine the role of mesenteric lymph reperfusion (MLR) on endotoxin translocation in brain to discuss the mechanism of brain injury subjected to superior mesenteric artery occlusion (SMAO) shock. METHODS: Twenty-four rats were randomly assigned to MLR, SMAO, MLR+SMAO and sham groups. MLR was performed by clamping the mesenteric lymph duct (MLD) for 1 h and then allowing reperfusion for 2 h in the MLR group; SMAO involved clamping the superior mesenteric artery (SMA) for 1 h, followed by reperfusion for 2 h in the SMAO group; occlusion of both the SMA and MLD for 1 h was followed by reperfusion for 2 h in the MLR+SMAO group rats. RESULTS: SMAO shock induced severe increased levels of the endotoxin, lipopolysaccharide receptor, lipopolysaccharide-binding protein, intercellular adhesion molecule-1 and tumor necrosis factor-α. Concurrently, MLR after SMAO shock further aggravates these deleterious effects. CONCLUSION: Mesenteric lymph reperfusion exacerbated the endotoxin translocation in brain; thereby increased inflammatory response occurred, suggesting that the intestinal lymph pathway plays an important role in the brain injury after superior mesenteric artery occlusion shock.
Asunto(s)
Traslocación Bacteriana/fisiología , Lesiones Encefálicas/etiología , Endotoxinas/fisiología , Vasos Linfáticos/fisiología , Oclusión Vascular Mesentérica/fisiopatología , Mesenterio , Daño por Reperfusión/fisiopatología , Proteínas de Fase Aguda/análisis , Animales , Lesiones Encefálicas/metabolismo , Proteínas Portadoras/análisis , Modelos Animales de Enfermedad , Endotoxinas/análisis , Ensayo de Inmunoadsorción Enzimática , Molécula 1 de Adhesión Intercelular/análisis , Ligadura , Receptores de Lipopolisacáridos/análisis , Vasos Linfáticos/cirugía , Masculino , Glicoproteínas de Membrana/análisis , Arteria Mesentérica Superior , Oclusión Vascular Mesentérica/complicaciones , Distribución Aleatoria , Ratas Wistar , Daño por Reperfusión/complicaciones , Factores de Tiempo , Factor de Necrosis Tumoral alfa/análisisRESUMEN
PURPOSE: To determine the role of mesenteric lymph reperfusion (MLR) on endotoxin translocation in brain to discuss the mechanism of brain injury subjected to superior mesenteric artery occlusion (SMAO) shock. METHODS: Twenty-four rats were randomly assigned to MLR, SMAO, MLR+SMAO and sham groups. MLR was performed by clamping the mesenteric lymph duct (MLD) for 1 h and then allowing reperfusion for 2 h in the MLR group; SMAO involved clamping the superior mesenteric artery (SMA) for 1 h, followed by reperfusion for 2 h in the SMAO group; occlusion of both the SMA and MLD for 1 h was followed by reperfusion for 2 h in the MLR+SMAO group rats. RESULTS: SMAO shock induced severe increased levels of the endotoxin, lipopolysaccharide receptor, lipopolysaccharide-binding protein, intercellular adhesion molecule-1 and tumor necrosis factor-α. Concurrently, MLR after SMAO shock further aggravates these deleterious effects. CONCLUSION: Mesenteric lymph reperfusion exacerbated the endotoxin translocation in brain; thereby increased inflammatory response occurred, suggesting that the intestinal lymph pathway plays an important role in the brain injury after superior mesenteric artery occlusion shock. .
Asunto(s)
Animales , Masculino , Traslocación Bacteriana/fisiología , Lesiones Encefálicas/etiología , Endotoxinas/fisiología , Vasos Linfáticos/fisiología , Mesenterio , Oclusión Vascular Mesentérica/fisiopatología , Daño por Reperfusión/fisiopatología , Proteínas de Fase Aguda/análisis , /análisis , Lesiones Encefálicas/metabolismo , Proteínas Portadoras/análisis , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Endotoxinas/análisis , Molécula 1 de Adhesión Intercelular/análisis , Ligadura , Vasos Linfáticos/cirugía , Arteria Mesentérica Superior , Glicoproteínas de Membrana/análisis , Oclusión Vascular Mesentérica/complicaciones , Distribución Aleatoria , Ratas Wistar , Daño por Reperfusión/complicaciones , Factores de Tiempo , Factor de Necrosis Tumoral alfa/análisisRESUMEN
To determine the role of mesenteric lymph reperfusion (MLR) on endotoxin translocation in brain to discuss the mechanism of brain injury subjected to superior mesenteric artery occlusion (SMAO) shock. Twenty-four rats were randomly assigned to MLR, SMAO, MLR+SMAO and sham groups. MLR was performed by clamping the mesenteric lymph duct (MLD) for 1 h and then allowing reperfusion for 2 h in the MLR group; SMAO involved clamping the superior mesenteric artery (SMA) for 1 h, followed by reperfusion for 2 h in the SMAO group; occlusion of both the SMA and MLD for 1 h was followed by reperfusion for 2 h in the MLR+SMAO group rats. SMAO shock induced severe increased levels of the endotoxin, lipopolysaccharide receptor, lipopolysaccharide-binding protein, intercellular adhesion molecule-1 and tumor necrosis factor-α. Concurrently, MLR after SMAO shock further aggravates these deleterious effects. Mesenteric lymph reperfusion exacerbated the endotoxin translocation in brain; thereby increased inflammatory response occurred, suggesting that the intestinal lymph pathway plays an important role in the brain injury after superior mesenteric artery occlusion shock.(AU)