Taken together, our results indicated that CD73 may facilitate the adhesion, migration and invasion of human breast cancer cells through its enzyme activity of generating adenosine. This study provided a possibly molecular mechanism of metastasis of breast carcinoma.
Ecto-5'-nucleotidase (CD73) was overexpressed in malignancies of epithelial origin and was involved in a variety of cellular processes such as cytoprotection and anti-inflammation. In the present study, human mammary T-47D cells were transfected with pcDNA-NT5E to establish a CD73 overexpressed cell model. Short small interfering RNA (siRNA) was used to silence the epidermal growth factor receptor (EGFR) gene. Real-time PCR, RT-PCR and western-blot were used to study CD73 and EGFR expression. Surface CD73 activity was assessed by quantifying the conversion of etheno-AMP to ethenoadenosine via HPLC. Interleukin (IL)-8 mRNA and protein expression were analyzed by RT-PCR and ELISA. Cell motility, invasiveness and adhesion to extracellular matrix (ECM) were measured by in vitro invasion and adhesion assay before and after transfection. We demonstrated that abilities of migration, invasions and adhesion to ECM in pcDNA-NT5E transfected T-47D cells increased significantly, which can be blocked by CD73 inhibitor alpha, beta-methylene ADP(APCP). Addition of adenosine reversed the effects of APCP. The mRNA and protein expression of EGFR and IL-8 increased in pcDNA-NT5E transfected T-47D cells. EGFR siRNA down-regulated EGFR expression dramatically, leading to migration and invasion activities inhibition in pcDNA-NT5E transfected T-47D cells. Our results suggest that up-regulated adenosine production, EGFR and IL-8 expression due to overexpressed CD73 may involved in CD73-promoted breast cancer metastasis.
♦ Results: In the 370 patients of the CQI group and the 249 patients of the control group, the predominant underlying kidney diseases were chronic glomerulonephritis and diabetic nephropathy. After implementation of the CQI initiative, the peritonitis rate declined to 1 episode in 77.25 patient-months from 1 episode in 22.86 patient-months. Ultrasound parameters of cardiac structure were generally unchanged in the CQI group, but significant increases in cardiothoracic ratio and interventricular septal thickness were observed in the control group (both p < 0.05). Patient survival at 1, 2, and 3 years was significantly higher in the CQI group (97.3%, 96.3%, and 96.3% respectively) than in the control group (92.6%, 82.4%, and 67.3% respectively, p < 0.001). Implementation of the CQI initiative also appeared to significantly improve technique survival rates: 95.6%, 92.6%, and 92.6% in the CQI group compared with 89.6%, 79.2%, and 76.8% in the control group (p < 0.001) after 1, 2, and 3 years respectively. ♦ Conclusion: Integration of a CQI process into a PD program can significantly improve the quality of therapy and its outcomes.Perit Dial Int 2014; 34(S2):S43-S48 www.PDIConnect.com
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