Objective To investigate the relationship between the expression of mast cell expressed membrane protein 1 (MCEMP1) in gastric cancer and its relationship with prognosis and tumor immune infiltration. Methods Transcriptome expression profile data and clinical data information of gastric cancer and normal samples were downloaded from TCGA database, and differentially expressed genes in gastric cancer tumor microenvironment were extracted using R 4.0.5 software. Protein-protein interaction network of differentially expressed genes was constructed by using STRING online website, protein-protein interaction network and univariate Cox proportional hazards regression analysis were used for cross-tabulation analysis to obtain key genes. Kruskal-Wallis rank sum test was used to investigate the correlation between key genes and clinicopathological features. The possible signaling pathways involved in key genes were predicted by gene set enrichment analysis. We further analyzed the relationship between expression of key gene and the level of immune infiltration and immune molecules in gastric cancer by TISIDB online database and CIBERSORT algorithm. Results A total of 760 differentially expressed genes in gastric cancer were found and a key gene of MCEMP1 was derived from cross-tabulation analysis based on the results of protein-protein interaction network and univariate Cox proportional hazards regression analysis. Expression of MCEMP1 was significantly upregulated in gastric cancer tissues (P<0.001), and survival analysis showed that the overall survival rate of the group with high expression level of MCEMP1 was lower than that of low expression [HR=1.176, 95%CI (1.066, 1.297）, P=0.046]. Expression of MCEMP1 also correlated with age, T-stage, and clinical stage of gastric cancer (P<0.05) , and expression of MCEMP1 was significantly associated with a variety kinds of immune cells and expression of immune molecules (P<0.05). Conclusion MCEMP1 is a potential prognostic marker for gastric cancer and is associated with immune infiltration in gastric cancer.
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 investigate the effect of Wnt5a derived from tumor-associated fibroblasts （CAFs） on the migration and invasion of gastric cancer cells. MethodsThe differentially expressed genes Wnt5a between CAFs and normal gastric fibroblasts (NGFs) in gastric cancer tissues and their corresponding normal gastric tissues using the GEO database GSE194261 dataset were screened. Immunohistochemical method was used to detect the expression of Wnt5a protein in tissue samples of clinical gastric cancer patients, and the relationship between Wnt5a protein expression and clinicopathological features of gastric cancer was analyzed. CAFs and NGFs were extracted from fresh surgical specimens of gastric cancer patients, and the expression of Wnt5a in CAFs was detected by real-time fluorescence quantitative-polymerase chain reaction and Western blot experiment. Transwell invasion and migration experiment was used to observe the effects of CAFs, inhibition of Wnt5a expression in CAFs and different concentrations of recombinant Wnt5a protein on the migration and invasion ability of gastric cancer MGC-803 and MKN-28 cell lines in vitro. ResultsThrough the screening of GEO database GSE194261 data set, it was found that Wnt5a was more expressed in CAFs than NGFs (P<0.05). Immunohistochemical results showed that the expression of Wnt5a protein in gastric cancer tissues was significantly stronger than that in normal gastric tissues (P<0.05), and the expression of Wnt5a protein was related to T stage of tumor (χ2=5.035, P<0.05), but not related to gender, age, degree of tumor differentiation, lymph node metastasis, vascular invasion and nerve invasion (P>0.05). Inhibiting Wnt5a derived from CAFs could inhibit the invasion and migration of gastric cancer cells. By stimulating gastric cancer cells with different concentrations of human recombinant Wnt5a protein, it was found that when the concentration of human recombinant Wnt5a protein was greater than 100 ng/mL, the invasion and migration abilities of MGC-803 and MKN-28 gastric cancer cells were significantly increased (P<0.05). ConclusionWnt5a is highly expressed in CAFs derived from the interstitial tissue of gastric cancer, which is related to the invasion depth of gastric cancer and can promote the invasion and migration of gastric cancer cells.
ObjectiveTo summarize the latest research progress and related mechanisms of cancer-associated fibroblasts (CAFs) in invasion, metastasis and drug resistance of breast cancer, so as to seek the best treatment strategy for patients with breast cancer metastasis and drug resistance. MethodThe literatures about CAFs research in breast cancer in recent years were searched and summarized. ResultsCAFs was the main stromal cell in tumor microenvironment (TME). By changing TME, the biological characteristics of CAFs could be changed and the growth and invasion of breast cancer cells could be induced. CAFs in breast cancer promotes the invasion and metastasis of breast cancer cells by interacting with inflammatory factors and promoting the formation of pre-transplantation ecosystems, and CAFs also mediates chemotherapy resistance to breast cancer, target resistance, endocrine resistance, and radiation resistance through the secretion of various cellular factors. ConclusionsAt present, some progress has been made in the research of CAFs in breast cancer, but there is still a certain gap to clinical application CAFs has a variety of functional phenotypes, so it is necessary to identify and characterize specific CAFs subtypes when studying new anti-CAFs therapeutic strategies. It has been proved that CAFs has great potential as a specific target for breast cancer treatment, but CAFs still lacks specific biomarkers. Therefore, an in-depth understanding of the biological characteristics and heterogeneity of CAFs can provide a reliable theoretical basis for developing drugs targeting CAFs.
Objective To summarize research status and mechanism about effects of carcinoma-associated fibroblasts (CAFs) on breast cancer stem cells. Method Relevant literatures about the relationship between the CAFs and breast cancer stem cells were collected and reviewed. Results CAFs were the majority type of the breast cancer stromal cells. The cancer stromal cell was also the important part of the tumor microenvironment, which could promote the proliferation, adhesion, invasion, and metastasis of the breast cancer. A subpopulation of cancer stem cells with the potentials of self-renewal and multi-directional differentiation in the breast cancer tissues might cause the tumor development. There was a phenotypic heterogeneity in the beast cancer stem cells, it was related to the tumor recurrence and therapy resistance. The CAFs could promote the formation of breast cancer stem cells through the epithelial mesenchymal transition and promote the transformation of tumor stem cell phenotype. More research needed to be done to prove these processes. Conclusion CAFs play an important role in formation of breast cancer stem cells and transformation of tumor stem cell phenotype, which might provide a new idea about treating breast cancer.
ObjectiveTo summarize the regulating mechanism of microRNA in tumor microenvironment. MethodThe literatures about the studies on the mechanism regulated by microRNA for tumor microenvironment were reviewed according to the results searched from PubMed in recent years. ResultsmicroRNA might be participated in regulation of tumor microenvironment factors such as hypoxia-inducible factor, tumor associated fibroblasts, extracellular matrix, which leaded to a change in biological behavior of tumor cells by reforming the microenviroment. ConclusionsmicroRNA has been participated in regulating many factors of tumor microenvironment. The change of neoplastic microenvironment has been recognized to play a critical role in the development of cancer. Therefore revealing microRNA mechanism for tumor microenvironment could not only help exploring the biological behavior of tumor cells, but also come an important insight for new means of diagnosis and treatment of cancer.
Objective To investigate relationship between hypoxia microenvironment and occurrence and development of hepatocellular carcinoma (HCC). Method The relevant literatures on researches of the relationship between the hypoxic microenvironment and the HCC were review and analyzed. Results The hypoxia microenvironment played an important role in inducing the drug resistance and angiogenesis of the HCC cells, and it was an important factor of affecting the ability of tumor metabolism, invasion, and migration. The hypoxia microenvironment could up-regulate the expression of hypoxia-inducible factors (HIFs) and promote its transcriptional activity, promote the expression of the vascular endothelial growth factor gene, and regulate the neovascularization in the tumor. Among them, the HIF-1α played a major role in regulating the angiogenesis, immune escape, tumor invasion and metastasis-related gene expression, participating in the glycolysis, regulating lysyl oxidase 2 and thus regulated epithelial-mesenchymal transition, then promoted the invasion and metastasis of the HCC; HIF-2α was a key regulator of the malignant phenotype involving in the cell proliferation, angiogenesis, apoptosis, metabolism, metastasis, and resistance to chemotherapy. The hypoxia microenvironment posed some difficulties for the treatment of HCC, but it was also a potential therapeutic breakthrough. Conclusion Hypoxia microenvironment can promote invasion and metastasis of HCC through various mechanisms, which provides new targets and strategies for clinical treatment of HCC.
In the tumor microenvironment, tumor-associated macrophage, as polarized macrophages M2 phenotype, can promote tumor progression and affect the prognosis of cancer. Significant attention has been drawn towards tumor-associated macrophage in recent years. In this review, we describe the polarization state of macrophages determined by tumor microenvironment and the recruitment of tumor-associated macrophage. We also pay special attention to the interaction between tumor-associated macrophages and tumors, discuss and summarize various targeted therapy strategies for tumor-associated macrophages, aiming to provide a reference for the future development of these novel and effective anti-cancer treatments.
ObjectiveTo investigate the effect of ubiquitin specific peptidase 22 (USP22) on the occurrence and development of esophageal squamous cell carcinoma (ESCC) under hypoxic conditions, and its regulatory relationship with hypoxia inducible factor-1α (HIF-1α). MethodsWestern blotting and quantitative polymerase chain reaction (qPCR) were used to detect the differences in USP22 protein and mRNA expression between normal esophageal epithelial cells HEEC and ESCC cell lines KYSE30, KYSE150, EC9706, and TE-1 under normoxic (5% CO2, 20% O2, 75% N2) and hypoxic (5% CO2, 1% O2, 94% N2) conditions. By transfecting USP22 plasmid or siUSP22, ESCC cells were divided into a normoxia control group, a normoxia+USP22 group, a normoxia+siUSP22 group, a hypoxia control group, a hypoxia+USP22 group, and a hypoxia+siUSP22 group. The proliferation and migration abilities of cells in each group were detected. The expression of USP22 and HIF-1α under hypoxic conditions after up-regulating or down-regulating USP22 was detected, and their regulatory relationship was verified. The interaction between USP22 and HIF-1α was verified by co-immunoprecipitation (Co-IP) technique. ResultsCompared with HEEC cells, the expression of USP22 in ESCC cells was significantly increased (P<0.05). Up-regulation of USP22 expression promoted the proliferation and migration of ESCC cells, while silencing USP22 inhibited the proliferation and migration of ESCC cells (P<0.05). Under hypoxic conditions, the expression of USP22 and HIF-1α increased, and with the up-regulation of USP22 expression, the expression of HIF-1α also significantly increased (P<0.05). Co-IP experiment confirmed the binding between USP22 and HIF-1α. ConclusionUp-regulation of USP22 expression promotes the proliferation and migration of ESCC cells. Hypoxia microenvironment can induce the increase of USP22 expression in ESCC. USP22 may participate in the regulation of the occurrence and development of ESCC by directly binding to HIF-1α.
Lung cancer has a high morbidity and mortality, and invasion is one of the major factors that cause recurrence and death in lung cancer patients. Tumor-associated macrophages (TAMs) are cells that have the potential to secrete cytokines, growth hormones, inflammatory substrates, and protein hydrolases, which are associated with the growth, invasion and metastasis of tumors. In this article, we will explore the various chemicals that are manufactured to promote the invasion of lung cancer, as well as the numerous clinical therapeutic features that TAMs possess in the treatment of lung cancer. In addition, we look at the possibility that TAMs might be beneficial in the treatment of lung cancer. We have an innovative investigation of the huge variety of complex substances generated by TAMs, with the goal of determining whether or not the molecules under investigation have the potential to serve as new therapeutic targets. Throughout the whole of the presentation, a significant focus is placed on doing in-depth research to ascertain whether TAMs have the capability to reinforce as viable carriers for unique and creative medications. This not only provides novel concepts for the creation of new targeted therapies but also leads to the development of brand-new, cutting-edge methods for the manufacture of individualized medicines and drug carriers.