Exosome-Derived ADAM17 Promotes Liver Metastasis in Colorectal Cancer.

Exosomes derived from cancer cells are deemed important drivers of pre-metastatic niche formation at distant organs, but the underlying mechanisms of their effects remain largely unknow. Although the role of ADAM17 in cancer cells has been well studied, the secreted ADAM17 effects transported via exosomes are less understood. Herein, we show that the level of exosome-derived ADAM17 is elevated in the serum of patients with metastatic colorectal cancer as well as in metastatic colorectal cancer cells. Furthermore, exosomal ADAM17 was shown to promote the migratory ability of colorectal cancer cells by cleaving the E-cadherin junction. Moreover, exosomal ADAM17 overexpression as well as RNA interference results highlighted its function as a tumor metastasis-promoting factor in colorectal cancer in vitro and in vivo. Taken together, our current work suggests that exosomal ADAM17 is involved in pre-metastatic niche formation and may be utilized as a blood-based biomarker of colorectal cancer metastasis.

[Studies on the cell markers of endothelial function in sepsis].

OBJECTIVE: To study the phasic changes of the number of circulating endothelial cells (CEC) and endothelial microparticles (EMP) during the process of sepsis. METHODS: Thirty-one patients with sepsis were divided into mild group (<9), moderate group (9-15) and severe group (>15) according to the acute physiology and chronic health evaluation II (APACHE II) scores after onset, and each group was further divided into survivors and non-survivors.The level of CEC, EMP and pro-inflammatory cytokines were determined on 1, 2, 3, 7, 14 days after onset. RESULTS: (1)The level of EMP, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) in the severe group were significantly higher than the mild group and moderate group (P<0.05 or P<0.01). The number of CEC in the severe group was significantly lower than the mild group and moderate group (P<0.05 or P<0.01). (2)The levels of CEC, EMP in the non-survivor and the survivor group were significantly higher with sepsis increased significantly; and the levels of EMP, pro-inflammatory in the non-survivor group were significantly higher than those of the survivor group (P<0.05 or P<0.01), but the levels of CEC, IL-4 and IL-10 in non-survivors were significantly lower than the survivors (P<0.05 or P<0.01). CONCLUSION: The levels of CEC and EMP in patients with sepsis increased significantly. They can not only serve as an index to reflect the severity of sepsis, but also have a prognostic value in patients with sepsis.