Increased pressure stimulates aberrant dendritic cell maturation

Cellular & Molecular Biology Letters

Keri L. Schaubert²  David H. Craig¹  Marc D. Basson⁴  Hiroe Shiratsuchi³  June Kan-Mitchell² 

[1] Department of Surgery, John D. Dingell VA Medical Center and Wayne State University, Detroit, USA$$Karmanos Cancer Institute, John D. Dingell VA Medical Center and Wayne State University, Detroit, USA$$;Karmanos Cancer Institute, John D. Dingell VA Medical Center and Wayne State University, Detroit, USA$$;Department of Surgery, John D. Dingell VA Medical Center and Wayne State University, Detroit, USA$$;Department of Surgery, John D. Dingell VA Medical Center and Wayne State University, Detroit, USA$$Department of Anesthesiology, John D. Dingell VA Medical Center and Wayne State University, Detroit, USA$$Department of Anatomy and Cell Biology, John D. Dingell VA Medical Center and Wayne State University, Detroit, USA$$Karmanos Cancer Institute, John D. Dingell VA Medical Center and Wayne State University, Detroit, USA$$

关键词: Pressure;    Dendritic cell;    Maturation;    Cancer;    Immunosurveillance;   

DOI  :  10.2478/s11658-007-0054-6

学科分类：分子生物学，细胞生物学和基因

来源: Uniwersytet Wroclawski * Wydzial Biotechnologii / University of Wroclaw, Faculty of Biotechnology

【 摘 要 】

Patients with malignancy typically exhibit abnormal dendritic cell profiles. Interstitial tumor pressure is increased 20-50mmHg over that in normal tissue. We hypothesized that elevated pressure in the tumor microenvironment may influence dendritic cell (DC) phenotype and function. Monocyte-derived immature and mature DC isolated from healthy human donors were exposed to either ambient or 40 mmHg increased pressure at 37°C for 12 hours, then assessed for expression of CD80, CD86, CD83, CD40, MHC-I and MHC-II. IL-12 production and phagocytosis of CFSE-labeled tumor lysate were assessed in parallel. Elevated pressure significantly increased expression of all co-stimulatory and MHC molecules on mature DC. Immature DC significantly increased expression of CD80, CD86, CD83 and MHC-II, but not MHC-I and CD40, versus ambient pressure controls. Pressure-treated immature DC phenotypically resembled mature DC controls, but produced low IL-12. Phenotypic maturation correlated with decreased phagocytic capacity. These results suggest increased extracellular pressure may cause aberrant DC maturation and impair tumor immunosurveillance.

【 授权许可】

Unknown