Hypoxic microenvironment always exists in solid tumors, and it closely relates to the development and metastasis of solid tumor. As a main transcription factor responding to hypoxic environment, hypoxia-inducible factor (HIF) can promote tumor cell proliferation, survival, angiogenesis, and epithelial-mesenchymal transition (EMT), etc. EMT is a biological process that epithelial phenotype was transformed into mesenchymal phenotype, which is mainly associated with its signaling pathways, transcription factors, inflammatory factors and miRNAs, and plays a vital role in tumor invasion and metastasis. This paper summarizes the effects of hypoxia signaling pathway, Wnt/β-catenin signaling pathway, Notch signaling pathway, NF-κB signaling pathway, Hedgehog (Hh) signaling pathway and PI3K/Akt signaling pathway on the EMT of tumor cells.
Objective To introduce the inflammatory microenvironment and epithelial-mesenchymal transition process of hepatocellular carcinoma, and review the relationship between them. Methods Domestic and international literatures were collected to summary the relationship between epithelial-mesenchymal transition and the inflammatory microenvironment of hepatocellular carcinoma. Result Many inflammatory factors and viral gene encoding proteins in the inflammatory microenvironment play an important role in the process of epithelial-mesenchymal transition in hepatocellular carcinoma. Conclusions The inflammatory microenvironment of hepatocellular carcinoma is an indispensable role in the process of epithelial-mesenchymal transition. The inhibition and treatment of inflammatory microenvironment may play a more active role in the control of tumor invasion and metastasis.
ObjectiveTo understand current research progress of microRNA (miRNA) in pathogenesis of triple-negative breast cancer (TNBC), and to provide reference for understanding pathogenesis and treatment of TNBC.MethodTheresearch progress of relationship of TNBC and miRNA was reviewed by reading relevant literatures at home and abroad in recent years.ResultsThe miRNAs were involved in a variety of biological processes, including the cell proliferation, apoptosis, autophagy, differentiation, metastasis, etc., and played an important role in the cancer initiation and metastasis. Therefore, researchers had attempted to treat and prevent the TNBC by targeting miRNAs. At present, there had been a large number of reports that the miRNAs played a key role in TNBC, which were classified as the anti-oncogene and oncogene, and was associated with metastasis and prognosis of TNBC.ConclusionmiRNA is very important in pathogenesis of TNBC. Mechanism of studying miRNA is necessary for treatment and prevention of TNBC.
This study aims to investigate the effect of substances secreted or metabolized by vascular endothelial cells on epithelial-mesenchymal transition (EMT) of hepatocellular carcinoma cells under indirect co-culture condition. Human hepatocellular carcinoma cell line QGY-7703 was cultured in vitro, and then was co-cultured with conditioned medium of human umbilical vein endothelial cells (HUVEC). The morphological changes of QGY-7703 cells were observed by inverted phase contrast microscopy. The migration ability of QGY-7703 cells was analyzed by scratch-wound assays. The effect of conditioned medium on the expression and distribution of EMT related proteins was detected by Western blot and immunofluorescence assays, respectively. The results showed that the QGY-7703 cells gradually changed from polygonal to spindle shape, the migration ability promoted significantly, and both the expression and distribution of EMT related marker changed in a time-dependent manner after co-culturing. The results confirm that vascular endothelial cells can induce EMT in hepatocellular carcinoma cells under indirect co-culture condition.
ObjectiveTo understand the research progress of the matrix metalloproteinases (MMPs) family in regulating the development of hepatocellular carcinoma (HCC) and its mechanism, in order to provide a reference for the basic research and clinical diagnosis and treatment of HCC. MethodThe relevant literature on the regulation of HCC occurrence, development, and mechanisms by MMPs both domestically and internationally in recent years was reviewed. ResultsThe extracellular matrix (ECM) microenvironment of HCC cells determined the invasiveness and degree of metastasis of tumor cells. The degradation and remodeling of ECM during epithelial mesenchymal transition (EMT) were the main factors contributing to the invasion and metastasis of HCC. The abnormal expression of most members of the MMPs family could lead to ECM breakdown, cell invasion and attachment, and markedly accelerate the process of EMT, thereby promoting the invasion and metastasis of HCC cells. At present, there were many MMPs related to the development of HCC, including MMP-1, 2, 3, 7, 9, 12, 13, 14. The relevant research on the relation between MMP-8, 10, 11, 15, 16, 20, 21, 26 or 28 and the development of HCC was relatively limited, while the exact research on the relationship between the MMP-17, 19, 23, 24, 25 or 27 and HCC development had not been retrievaled. ConclusionsThe MMPs family members (especially MMP-2, 3, 7, 9, 10, 12) play a crucial role in the progression of HCC, including proliferation, invasion, and metastasis. Further exploration of the potential intrinsic relation between all members of the MMPs family members and the development of HCC is crucial for predicting HCC metastasis potentiality and prognosis, as well as developing new or improved targeted anti-cancer therapies for HCC.
ObjectiveTo investigate the effect of succinate induced polarization of MH-S murine alveolar macrophage cells on hyperoxia-induced epithelial-mesenchymal transition (EMT) of MLE-12 mouse alveolar epithelial cells. Methods Determine the exposure time: MLE-12 cells was cultured in an incubator with 95%O2 for different time to establish a cell model of acute hyperoxia-induced lung injury. The relative expression of EMT-related proteins (E-cadherin, N-cadherin, vimentin) was determined by Western blotting. Co-culture of MLE-12 and MH-S to explore the influence of MH-S on EMT: MLE-12 was divided into hyperoxia group for 0h, hyperoxia group for 48h and co-cultured with MH-S hyperoxia group for 48h (Co). The relative expression of EMT-related proteins was determined by Western blotting. Determination of succinate concentration and its effect on MH-S polarization and succinate receptor GPR91: MLE-12 was cultured in different concentrations of succinate medium for 24h, and the cell viability was determined by CCK-8. MH-S was divided into control group (C) and succinate group (S). Group C was cultured for 24h, and group S was added with succinate at the above concentration. The relative expression of GPR91 and polarization-related factor mRNA in MH-S was measured by RT-qPCR, and the expression of macrophage polarization-related proteins (CD11b, CD206, CD86) was measured by flow cytometry. Study on the effect of succinate on EMT by cell co-culture: MLE-12 and MH-S were co-cultured in a Transwell chamber and divided into control group (Co), succinate group (SUC) and GPR91 inhibitor group (I). Results Expression of EMT-related proteins in four groups of MLE-12 at different times: Compared with 0h, the expression of vimentin and N-cadherin in 24h and 48h increased, while the expression of E-cadherin in 48 h and 72 h decreased (P<0.05), and there was no significant difference in other groups. The follow-up experiment was conducted under hyperoxia conditions for 48h. Influence of MH-S on EMT: The expression of vimentin and N-cadherin in Co group was higher than that in 48h, and the expression of E-cadherin was lower than that in 48h (P<0.05). After 24 h of intervention with different concentrations of succinate on MLE-12, compared with the 0mmol/L, the cell viability of 2.5mmol/L, 1mmol/L and 500 μmol/L increased (P<0.05), and there was no significant difference in other groups, so the 1mmol/L succinate concentration was selected for subsequent experiment. Compared with group C, the expression of GPR91 mRNA in group S increased, and the expression of iNOS and CD86 mRNA in group S increased (P<0.05), but there was no significant difference in other groups. The analysis of flow cytometry showed that 1mmol/L succinate could increase the number and proportion of CD86+CD206– alveolar macrophages. Compared with Co group, the expression of vimentin and N-cadherin in SUC group increased, while the expression of E-cadherin decreased. Compared with SUC group, the expression of vimentin and N-cadherin in group I decreased, while the expression of E-cadherin increased (P<0.05). Conclusion Succinate can induce mouse alveolar macrophages polarization to M1 through GPR91, enhance EMT of mouse alveolar epithelial cell injury model under hyperoxia, and promote the formation of pulmonary fibrosis.