ABSTRACT
Leukemia inhibitory factor receptor (LIFR) has been documented as a cancer promoter and to be present at high levels in various types of tumor tissues. In our search for molecules prognostic of colorectal cancer (CRC), we found high levels of LIFR in CRC tissue samples. Further analyses revealed that LIFR was indeed prognostic of CRC patient survival, and was associated with tumor size, lymphatic metastasis and stages. LIFR was found to promote tumor growth, metastasis and angiogenesis both in vitro and in vivo. High levels of LIFR in CRC facilitated proliferation and migration of endothelial cells, resulting in an increase in angiogenic activity. Moreover, interleukin 8 (IL-8) was found to play a role in the LIFR induced angiogenesis. IL-8 levels were correlated with LIFR levels in CRC tissues, whereas depletion of IL-8 led to a reduced angiogenic activity of LIFR in CRC cells. In addition, LIFR increased phosphorylation level of Erk, which regulates il-8 transcription. We conclude that LIFR is possibly a valuable prognostic marker for CRC. Our results also implicate a mechanism by which LIFR regulates tumor angiogenesis through Erk/IL-8 pathway, and that LIFR could be a potential therapeutic target for CRC.
Subject(s)
Colorectal Neoplasms/blood supply , Endothelial Cells/pathology , Interleukin-8/metabolism , Leukemia Inhibitory Factor Receptor alpha Subunit/metabolism , Neovascularization, Pathologic/pathology , Aged , Animals , Biomarkers, Tumor/metabolism , Cell Line, Tumor , Cell Proliferation , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Down-Regulation , Female , Follow-Up Studies , Human Umbilical Vein Endothelial Cells , Humans , Interleukin-8/genetics , Leukemia Inhibitory Factor Receptor alpha Subunit/genetics , Male , Mice , Mice, Nude , Middle Aged , Neovascularization, Pathologic/mortality , Prognosis , RNA, Small Interfering/metabolism , Up-Regulation , Xenograft Model Antitumor AssaysABSTRACT
Studies indicate that the chemokine receptor is responsible for poor prognosis of hepatocellular carcinoma (HCC) patients. In this study, we initially demonstrated that CCR4 is overexpressed in HCC specimens, and its elevation in HCC tissues positively correlates with tumor capsule breakthrough and vascular invasion. Although overexpression of CCR4 failed to influent proliferation of HCC cells in vitro apparently, the prominent acceleration on HCC tumor growth in vivo was remarkable. The underlying mechanism may be involved in neovascularization. Interestingly, different from effect on proliferation, CCR4 overexpression could trigger HCC metastasis both in vitro and in vivo also induced HCC cell epithelial-mesenchymal transition (EMT) as well. Then we identified matrix metalloproteinase 2 (MMP2) as a direct target of CCR4 which plays an important role in CCR4-mediated HCC cell invasion, which was up-regulated by ERK/AKT signaling. Positive correlation between CCR4 and MMP2 expression was also observed in HCC tissues. In conclusion, our study suggested that chemokine receptor CCR4 promotes HCC malignancy and facilitated HCC cell metastases via ERK/AKT/MMP2 pathway. These findings suggest that CCR4 may be a potential new diagnostic and prognostic marker in HCC, and targeting CCR4 may be a potential therapeutic option for blocking HCC metastasis.
Subject(s)
Carcinoma, Hepatocellular/genetics , Liver Neoplasms/genetics , Receptors, CCR4/genetics , Transplantation, Heterologous , Up-Regulation , Adult , Aged , Aged, 80 and over , Animals , Carcinoma, Hepatocellular/metabolism , Cell Line, Tumor , Epithelial-Mesenchymal Transition/genetics , Female , Gene Expression Regulation, Neoplastic , Hep G2 Cells , Humans , Liver Neoplasms/metabolism , Male , Mice, Inbred BALB C , Mice, Nude , Middle Aged , Receptors, CCR4/metabolism , Tumor Burden/geneticsABSTRACT
Objective To investigate the effects of formative assessment in teaching histology .Methods Multiple methods were used , including homework , self-test and quiz , questionnaire survey and so on , to evaluated teaching process .Collected data were analyzed statistically .Results Autonomous homework was welcomed by students:89.8%of the students believed that homework was necessary , and nearly half of them thought they got profit from this.Students who completed the self-tests more got higher score in the final exam than those who completed less . Questions with high error rate in quiz got higher accuracy in the final exam .Students thought their ability , especially the autonomous learning ability , improved during the learning process .Conclusions Both teachers and students got profit in the aspects of knowledge , ability and emotion from introducing formative assessment into teaching and learn -ing process .Quality of teaching histology would be improved through better assessment methods and means .
