ABSTRACT
Objective To explore the features of peripheral blood immune cells in long-term survival recipients after liver transplantation.Methods The expression of T subsets (Th1,Th2,Th17,Th22,Tregs),NK cells,NKt cells,Bregs,MDSC in long-term survival recipients (postoperative follow-up time ≥5 years,30 cases),short-term survival recipients(postoperative follow-up time ≤1 year,15 cases) and healthy control (15 cases) were determined by flowcytometry.Results Th17 cells were significantly higher in the long-term group compared with short-term group and healthy control group(P ＜0.01).Tregs in long-term group compared with short-term group were significantly higher (P ＜ 0.01),but the difference was not statistically significant compared with healthy control group (P ＞ 0.05).NK cells were significantly higher in long-term group compared with short-term group and healthy control group (P ＜ 0.01).MDSC were significantly higher in long-term group compared with short-term group and healthy control group (P ＜0.01).Conclusions Th17,Tregs,NK cells and MDSC were significantly higher in long-term survival of liver recipients,which may be related to immune tolerance.
ABSTRACT
Cancer progression is governed by multifaceted interactions of cancer cells with their microenvironment and one of these ways is through secreted compounds. Substances released by gastric cancer cells have not being profiled in a proteome-wide manner. ITRAQ-based tandem mass spectrometry was employed to quantify proteins secreted by HFE145 normal, MKN7 well-differentiated, and MKN45 poorly differentiated gastric cancer cell lines. The expression levels of 237 proteins were found to be significantly different between normal and cancer cells. Further examination of 16 gastric cell lines and 115 clinical samples validated the up-regulation of CTSS expression in gastric cancer. Silencing CTSS expression suppressed the migration and invasion of gastric cancer cells in vitro. Subsequent secretomics revealed that CTSS silencing resulted in changes in expression levels of 197 proteins, one-third of which are implicated in cellular movement. Proteome-wide comparative secretomes of normal and gastric cancer cells were produced that constitute a useful resource for gastric cancer research. CTSS was demonstrated to play novel roles in gastric cancer cell migration and invasion, putatively via a network of proteins associated with cell migration, invasion, or metastasis. Cathepsin S is member of a large group of extracellular proteases, which are attractive drug targets. The implicated role of CTSS in gastric cancer metastasis provides an opportunity to test existing compounds against CTSS for adjuvant therapy and/or treatment of metastatic gastric cancers.
Subject(s)
Cathepsins/metabolism , Cell Movement/physiology , Neoplasm Proteins/metabolism , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathology , Cathepsins/chemistry , Cell Line, Tumor , Humans , Isotope Labeling , Neoplasm Invasiveness , Neoplasm Proteins/chemistry , Proteomics/methods , Reproducibility of Results , Signal Transduction , Tandem Mass SpectrometryABSTRACT
Genetic aberration of EGFR is one of the major molecular characteristics of breast cancer. However, the molecular changes associated with EGFR signaling during different stages of breast cancer development have not been studied. In this study, complementary two-dimensional-DIGE and iTRAQ technologies were used to profile the expression level of proteins in 4 isogenic cell lines in the MCF10AT model of breast cancer progression following a time course of EGF stimulation. A total of 80 proteins (67 from iTRAQ, 15 from DIGE, 2 common in both) were identified to be up- or down-regulated by EGF treatment. Following EGF stimulation, the expression level of MIF, a cytokine that has been implicated in many human cancers, was decreased in MCF10A1 normal breast mammary epithelial cells, increased in MCF10AT1k preneoplastic and MCF10CA1h low grade breast cancer cells, but showed no obvious difference in the MCF10CA1a high grade cancer cells. The increase in MIF expression level following EGF treatment could also be observed in A431 cervical cancer cells. EGF-induced increases of MIF expression levels in CA1h breast cancer cells were abrogated when MEK, but not PIK3CA, was knocked down. In addition, silencing of MIF diminished the proliferation of EGF-stimulated CA1h cells when compared to control cells. Taken together, our data suggested an EGFR --> MEK --> MIF proliferative pathway that has never been reported previously and that this pathway "evolves" during disease progression as modeled by the MCF10AT system. Revelation of the novel relationship between MIF and EGF may contribute to an integrated understanding of the roles of these oncogenic factors during breast cancer development.
