Erratum: Circular RNA Hsa_circRNA_101996 promotes the development of Gastric Cancer via Upregulating Matrix Metalloproteinases-2/Matrix Metalloproteinases-9 through MicroRNA-143/Ten-eleven translocation-2 Pathway: Erratum.

[This corrects the article DOI: 10.7150/jca.62121.].

Tumor-associated macrophages promoting PD-L1 expression in infiltrating B cells through the CXCL12/CXCR4 axis in human hepatocellular carcinoma.

The inflammation-related tumor microenvironment (TME) is one of the major driving forces of hepatocarcinogenesis. We aimed to investigate cell-to-cell communication among Hepatocellular Carcinoma (HCC) through re-analyzing HCC single-cell RNA-seq data, and to confirm such cellular interaction through in vitro and in vivo study. We found a subset of Regulatory B cells with PD-L1 expression (PD-L1+ Bregs), mainly located in adjacent HCC tissues. In co-localization with PD-L1+ Bregs, a subset of Tumor Associated Macrophages with high expression of CXCL12 (CXCL12+ TAMs) was also mainly located in adjacent HCC tissues. Moreover, CXCL12+ TAMs can be stimulated in vitro using an HCC conditional medium. Using CellChat analysis and Multiplex Immunohistochemistry staining (mIHC), CXCL12+ TAMs were found to be first recruited by Cancer-Associated Fibroblasts (CAFs) through a CD74/macrophage migration inhibitory factor (MIF) pattern, and further differentiated into TGF-ß-enriched tissues. Furthermore, CXCL12+ TAMs recruited PD-L1+ Bregs via the CXCL12/CXCR4 axis, and CXCR4 expression was significantly positively correlated to PD-L1 expression in PD-L1+ Bregs. At last, we confirmed the communications among CAFs, Macrophages and B cells and their tumor-promoting effects by using an orthotopic mouse model of HCC. Immunosuppressive HCC TME involving cell-to-cell communications comprised MIF-secreting CAFs, CXCL12-secreting TAMs, and PD-L1-producing Bregs, and their regulation could be promising therapeutic targets in future immunotherapy for human HCC.

Cargoes of exosomes function as potential biomarkers for Mycobacterium tuberculosis infection.

Exosomes as double-membrane vesicles contain various contents of lipids, proteins, mRNAs and non-coding RNAs, and involve in multiple physiological processes, for instance intercellular communication and immunomodulation. Currently, numerous studies found that the components of exosomal proteins, nucleic acids or lipids released from host cells are altered following infection with Mycobacterium tuberculosis. Exosomal contents provide excellent biomarkers for the auxiliary diagnosis, efficacy evaluation, and prognosis of tuberculosis. This study aimed to review the current literatures detailing the functions of exosomes in the procedure of M. tuberculosis infection, and determine the potential values of exosomes as biomarkers to assist in the diagnosis and monitoring of tuberculosis.

The characteristics and the multiple functions of integrin ß1 in human cancers.

Integrins, which consist of two non-covalently linked α and ß subunits, play a crucial role in cell-cell adhesion and cell-extracellular matrix (ECM) interactions. Among them, integrin ß1 is the most common subunit and has emerged as a key mediator in cancer, influencing various aspects of cancer progression, including cell motility, adhesion, migration, proliferation, differentiation and chemotherapy resistance. However, given the complexity and sometimes contradictory characteristics, targeting integrin ß1 for therapeutics has been a challenge. The emerging understanding of the mechanisms regulating by integrin ß1 may guide the development of new strategies for anti-cancer therapy. In this review, we summarize the multiple functions of integrin ß1 and signaling pathways which underlie the involvement of integrin ß1 in several malignant cancers. Our review suggests the possibility of using integrin ß1 as a therapeutic target and highlights the need for patient stratification based on expression of different integrin receptors in future clinical studies.

Mesenchymal stem/stromal cells- a principal element for tumour microenvironment heterogeneity.

The heterogeneity of the tumor microenvironment (TME) is a major obstacle in cancer treatment, making most therapeutic interventions palliative rather than curative. Previous studies have suggested that the reason for the low efficacy of immunotherapy and the relapse of the original responders over time may be due to the complex network of mesenchymal stem/stromal cells (MSCs), a population of multipotent progenitor cells existing in a variety of tissues. Cancer-associated MSCs (CA-MSCs) have already been isolated from various types of tumors and are characterized by their vigorous pro-tumorigenic functions. Although the roles of CA-MSCs from different sources vary widely, their origins are still poorly understood. Current evidence suggests that when local resident or distally recruited MSCs interact with tumor cells and other components in the TME, "naïve" MSCs undergo genetic and functional changes to form CA-MSCs. In this review, we mainly focus on the multiple roles of CA-MSCs derived from different sources, which may help in elucidating the formation and function of the entire TME, as well as discover innovative targets for anti-cancer therapies.

Hsa_circ_0073453 modulates IL-8 secretion by GC-MSCs to promote gastric cancer progression by sponging miR-146a-5p.

Gastric cancer associated mesenchymal stem cells (GC-MSCs) have been demonstrated to promote gastric cancer progression in a paracrine manner. IL-8 is highly secreted by GC-MSCs and is crucial for their oncogenic function. However, the mechanism underlying the modulation of IL-8 secretion by GC-MSCs has not been well elucidated. In this study, Shbio-human ceRNA array was used to identify dysregulated mRNAs and circRNAs between GC-MSCs and bone marrow derived mesenchymal stem cells (BM-MSCs). IL-8 was validated to be a critical paracrine cytokine for GC-MSCs promoting migration and invasion of gastric cancer cells. circ_0073453 was identified as a novel GC-MSC-derived circRNA which acted as a sponge of miR-146a-5p, thus increasing IL-8 expression and secretion to promote gastric cancer cell metastasis. Furthermore, circ_0073453 modulated IL-8 secretion by GC-MSCs to enhance gastric cancer cells PD-L1 expression to resist cytotoxic CD8+ T cell-killing. circ_0073453/miR-146a-5p/IL-8 axis was deregulated in gastric cancer tissues and associated with prognosis depending on MSC abundance in cancer tissues. Taken together, our findings suggest that circ_0073453/miR-146a-5p/IL-8 axis is critical for GC-MSCs promoting gastric cancer progression. Hence, hsa_circ_0073453 may be a potential therapeutic target for gastric cancer.

Exosomal CD44 Transmits Lymph Node Metastatic Capacity Between Gastric Cancer Cells via YAP-CPT1A-Mediated FAO Reprogramming.

Background: Lymph node metastasis (LNM) commonly occurs in gastric cancer (GC) and is tightly associated with poor prognosis. Exosome-mediated lymphangiogenesis has been considered an important driver of LNM. Whether exosomes directly transmit the LNM phenotype between GC cells and its mechanisms remain elusive. Methods: A highly lymphatic metastatic GC cell line (HGC-27-L) was established by serial passage of parental HGC-27 cells in BALB/c nude mice. The capacities of migration, invasion and LNM; fatty acid oxidation (FAO) levels; and the role of exosome-transferred LNM phenotype were compared among HGC-27-L, HGC-27 and primary GC cell line AGS. Exosomes derived from GC cells and sera were separately isolated using ultracentrifugation and ExoQuick exosome precipitation solution, and were characterized by transmission electron microscopy, Nanosight and western blotting. Transwell assay and LNM models were conducted to evaluate the capacities of migration, invasion and LNM of GC cells in vitro and in vivo. ß-oxidation rate and CPT1 activity were measured to assess FAO. CPT1A inhibitor etomoxir was used to determine the role of FAO. Label-free LC-MS/MS proteome analysis screened the differential protein profiling between HGC-27-exosomes and AGS-exosomes. Small interference RNAs and YAP inhibitor verteporfin were used to elucidate the role and mechanism of exosomal CD44. TCGA data analysis, immunochemistry staining and ELISA were performed to analyze the expression correlation and clinical significance of CD44/YAP/CPT1A. Results: FAO was increased in lymphatic metastatic GC cells and indispensable for sustaining LNM capacity. Lymphatic metastatic GC cell-exosomes conferred LNM capacity on primary GC cells in an FAO-dependent way. Mechanistically, CD44 was identified to be enriched in HGC-27-exosomes and was a critical cargo protein regulating exosome-mediated transmission, possibly by modulating the RhoA/YAP/Prox1/CPT1A signaling axis. Abnormal expression of CD44/YAP/CPT1A in GC tissues was correlated with each other and associated with LNM status, stages, invasion and poor survival. Serum exosomal CD44 concentration was positively correlated with tumor burden in lymph nodes. Conclusions: We uncovered a novel mechanism: exosomal CD44 transmits LNM capacity between GC cells via YAP-CPT1A-mediated FAO reprogramming from the perspective of exosomes-transferred LNM phenotype. This provides potential therapeutic targets and a non-invasive biomarker for GC patients with LNM.

Circular RNA Hsa_circRNA_101996 promotes the development of Gastric Cancer via Upregulating Matrix Metalloproteinases-2/Matrix Metalloproteinases-9 through MicroRNA-143/Ten-eleven translocation-2 Pathway.

Background: The long-term survival rate of gastric cancer (GC) patients at advanced stages remains low worldwide. Circular RNAs (circRNAs) a newly studied type of non-coding RNA that play an important role in the pathogenesis and diagnosis of various diseases. In this research, we aimed to explore the functions of hsa_circRNA_101996 in GC cells and an animal model of GC. Methods: The expression of hsa_circRNA_101996, microRNA (miR)-143, and ten-eleven translocation (TET)-2 in GC tissues, the adjacent tissues, and cell lines were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Transwell assays were used to analyze the knockdown effects of hsa_circRNA_101996, miR-143, and overexpression of TET2 on cell proliferation, migration, and invasion abilities. Western blotting was used to analyze the expression of matrix metalloproteinases (MMP)2/MMP9. Binding interactions between, hsa_circRNA_101996 and miR-143 and between, miR-143 and TET2 were detected by Dual-luciferase reporter assays. Levels of protein expression were analyzed by Western blotting. Tumor models were established by subcutaneous injection of tumor cells in Bl6/Rag2/GammaC double knockout mice. Results: The result showed that hsa_circRNA_101996 expression was significantly upregulated in GC tissues compared to that in the adjacent tissues, and its level in cancer tissue was correlated with tumor size, lymphatic metastasis, and distant metastasis. Compared with the low hsa_circRNA_101996 expression group, the three-year survival rate of patients in the high hsa_circRNA_101996 expression group was significantly lower. The knockdown of hsa_circRNA_101996 dramatically suppressed the cell migration, invasion, and proliferation of GC cells by sponging to absorb miR-143 and elevated the expression of TET2. In vivo studies showed that the knockdown of hsa_circRNA_101996 delayed tumor growth. Furthermore, we revealed that TET2 regulates MMP2/MMP9 expression through the DNA demethylation pathway. Conclusion: Our findings indicate that hsa_circRNA_101996 promotes GC development by upregulating MMP2/MMP9 through miR-143/TET2 pathway, which may provide a novel target for GC.

Leptin induces NAFLD progression through infiltrated CD8+ T lymphocytes mediating pyroptotic-like cell death of hepatocytes and macrophages.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease, which causes serious health problems worldwide. Hyperleptinemia and inflammatory stress are crucial in the progression of NAFLD. However, the relationship between leptin and immune cells or hepatocytes is still unclear. AIMS: This study aimed to clarify the regulatory mechanism of leptin-mediated disease progression through immune cells and its relationship with hepatocytes. METHODS: An NAFLD rat model was established to verify the relationship between hyperleptinemia and CD8+ T lymphocytes and cytokines in liver tissue. CD8+ T lymphocytes isolated from blood mononuclear cells were co-cultured with macrophages or hepatocytes stimulated with leptin or treated with granzyme inhibitors to observe target cell morphology and expression of pivotal protein family members. RESULTS: CD8+ T lymphocyte infiltration positively correlated with blood leptin, IL-18 and IL-1ß levels and was related to macrophage recruitment and differentiation in a rat model of NAFLD. Leptin could induce activated caspase-1 and caspase-3 in hepatocytes and trigger hepatocyte pyroptosis. CONCLUSIONS: Leptin may regulate the pyroptotic-like death of macrophages and hepatocytes through CD8+ T lymphocytes in NAFLD progression. The intervention of related pathways of leptin and immune cells may provide a promising strategy for treating NAFLD.

RP11-323N12.5 promotes the malignancy and immunosuppression of human gastric cancer by increasing YAP1 transcription.

BACKGROUND: YAP1 is a core protein of the Hippo signaling pathway and is associated with malignancy and immunosuppression. In the present study, we discovered a novel lncRNA, RP11-323N12.5, with tumor promotion and immunosuppression activities through enhancing transcription of YAP1. METHODS: RP11-323N12.5 was identified using GEPIA. Its expression levels and their relationship with clinical features were investigated using clinical samples. The regulation of YAP1 transcription by RP11-323N12.5 was investigated in both GC and T cells, the tumor and immunosuppression promotion roles of RP11-323N12.5 were explored in vitro and in vivo. RESULTS: RP11-323N12.5 was the most up-regulated lncRNA in human GC, based on data from the TCGA database. Its transcription was significantly positively correlated with YAP1 transcription, YAP1 downstream gene expression which contribute to tumor growth and immunosuppression. RP11-323N12.5 promoted YAP1 transcription by binding to c-MYC in the YAP1 promoter region. Meanwhile, transcription of RP11-323N12.5 was also regulated by YAP1/TAZ/TEADs activation in GC cells. RP11-323N12.5 had tumor- and immnosuppression-promoting effects by enhancing YAP1 downstream genes in GC cells. Excessive RP11-323N12.5 was also observed in tumor-infiltrating leukocytes (TILs), which may be exosome-derived and also be related to enhanced Treg differentiation as a result YAP1 up-regulation. Moreover, RP11-323N12.5 promoted tumor growth and immunosuppression via YAP1 up-regulation in vivo. CONCLUSIONS: RP11-323N12.5 was the most up-regulated lncRNA in human GC and it promoted YAP1 transcription by binding to c-MYC within the YAP1 promoter in both GC and T cells. RP11-323N12.5 is an ideal therapeutic target in human GC due to its tumor-promoting and immunosuppression characteristics.

IL-6 promotes PD-L1 expression in monocytes and macrophages by decreasing protein tyrosine phosphatase receptor type O expression in human hepatocellular carcinoma.

BACKGROUND: We have previously discovered a relationship between the low expression of protein tyrosine phosphatase, receptor type O (PTPRO) in tumor-infiltrating T cells and immunosuppression. The aim of the present study was to investigate the relationship between decreased PTPRO and increased programmed death ligand 1 (PD-L1) in both the peripheral monocytes and tumor-infiltrating macrophages of human hepatocellular carcinoma (HCC). METHODS: The expression and correlation of all the indices were explored in monocytes and tumor-infiltrating macrophages within both human and mice HCC. The mechanic regulations were studied by using both in vitro and in vivo studies. RESULTS: We found a significant decrease in PTPRO in HCC peripheral monocytes that was associated with increased PD-L1 expression in peripheral monocytes and tumor-associated macrophages (TAMs) in HCC. Monocyte PD-L1 and PTPRO therefore could serve as valuable prognostic indicators for post-surgery patients with HCC and were associated with increased T-cell exhaustion (Tim3+T cells). A depletion of PTPRO promoted PD-L1 secretion in both monocytes and macrophages through the JAK2/STAT1 and JAK2/STAT3/c-MYC pathways. Increased IL-6 expression was associated with activation of JAK2/STAT3/c-MYC and with decreased PTPRO expression through the STAT3/c-MYC/miR-25-3 p axis. Monocytes and TAMs showed significantly increased miR-25-3 p expression, which could target the 3' untranslated region of PTPRO. The miR-25-3 p expression positively correlated with serum IL-6 levels, but inversely correlated with PTPRO in HCC monocytes. IL-6/STAT3/c-MYC activation enhanced in vitro miR-25-3 p transcription and decreased PTPRO, while further promoting PD-L1 secretion. Adoptive cell transfer of c-MYC/miR-25-3 p-modified monocytes promoted tumor growth by downregulating PTPRO and causing a PD-L1-induced immunosuppression in an orthotopic tumor transplantation model. CONCLUSIONS: Increased serum IL-6 downregulated PTPRO expression in HCC monocytes and macrophages by activating STAT3/c-MYC/miR-25-3 p and by further enhancing PD-L1 expression through JAK2/STAT1 and JAK2/STAT3/c-MYC signaling.

Interaction of transforming growth factor-ß-Smads/microRNA-362-3p/CD82 mediated by M2 macrophages promotes the process of epithelial-mesenchymal transition in hepatocellular carcinoma cells.

Abnormal tumor microenvironment and the epithelial-mesenchymal transition (EMT) are important features of tumor metastasis. However, it remains unknown how signals can form complicated networks to regulate the sustainability of the EMT process. The aim of our study is to explore the possible interaction between tumor-associated macrophages and tumor cells in the EMT process mediated by microRNA (miR)-362-3p. In this study, we found that by releasing TGF-ß, M2 macrophages mediate binding of Smad2/3 to miR-362-3p promoter, leading to overexpression of miR-362-3p. MicroRNA-362-3p maintains EMT by regulating CD82, one of the most important members of the family of tetraspanins. Our finding suggests that miR-362-3p can serve as a core factor mediating cross-talk between the TGF-ß pathway in tumor-associated macrophages and tetraspanins in tumor cells, and thus facilitates the EMT process.

Inflammatory responses induced by Helicobacter pylori on the carcinogenesis of gastric epithelial GES­1 cells.

Helicobacter pylori (HP) is a pathogenic bacterium associated with chronic gastritis, gastric ulcer and gastric cancer. In the present study, the primary carcinogenesis process of normal gastric epithelial cells (GES­1) infected with HP was investigated. It was determined that infected gastric mucosal epithelial GES­1 cells secreted increased interleukin­8 (IL­8) and IL­23, and exhibited enhanced expression of inducible nitric oxide synthase and cyclooxygenase­2, inducing inflammatory reactions and resulting in apoptosis. The bacterial infection significantly increased the expression of carcinogenesis­associated genes, including p16, c­Myc, p53 and p21, as well as the expression of cell surface signaling molecules cluster of differentiation 44 (CD44) and CD54 in GES­1 cells or tissues of patients with gastritis and gastric cancer in vitro or in vivo. Simultaneously, the migration and invasion abilities of normal gastric epithelial GES­1 cells were increased following HP infection. These observations demonstrated that the inflammatory response of HP infection could cause normal gastric epithelial cells to undergo significant cancerous reactions, indicating that HP is a risk factor for gastric cancer.

Host derived exosomes-pathogens interactions: Potential functions of exosomes in pathogen infection.

As bilayer vesicular corpuscles secreted by different living cells, exosomes can be found in diverse body fluids and are rich in lipids, proteins, nucleic acids and other complicated components. Exosomes offer a potent mechanism for participation in intercellular transportation, such as targeted transmission of inclusions to nearby or distant cells or tissues, and assistance in intercellular information communication to change physiological functions and properties. Exosomes take part in antigen presentation for activation of immune cells and stimulate the release of inflammatory factors and the expression of immune molecules, thus modulating the immune responses of host cells. In the microbial infection of host cells, exosomes can strengthen innate and specific immune responses and thereby the immune resistance against the invading microbes through natural killer cells, macrophages and activated T cells by the presentation of pathogens including viral factors and bacteria, but exosomes are also capable of immunosuppression during pathogens infection. Exosomes are considerably valuable in research and clinical defense of microbial infection, given their biological activities in intercellular transportation, information communication and cell-mediated immunity modulation after microbial infection.

A study on the roles of Helicobacter pylori in bile reflux gastritis and gastric cancer.

PURPOSE: To observe the infection rates of Helicobacter pylori (HP) in bile reflux gastritis (BRG) and gastric cancer and the clinical significance of HP eradication in BRG and gastric cancer patients complicated with HP. METHODS: 248 patients diagnosed with BRG and gastric cancer via gastroscopy were enrolled in this study. HP detection and infection rates of HP were evaluated. Then, BRG and gastric cancer patients complicated with HP were randomly divided into BRG group 1, BRG group 2, gastric cancer group 1 and gastric cancer group 2. BRG group 1 and gastric cancer group 1 were treated with conventional anti-inflammatory drugs for 10 days, and BRG group 2 and gastric cancer group 2 were treated with anti-HP drugs in addition to conventional anti-inflammatory drugs. One month after drug withdrawal, the infection rates of HP in each group were evaluated, and prognostic follow-up was performed to record the post-therapy patient conditions. RESULTS: HP infection rate was 35.8% (57/159) in the BRG group and 73.0% (65/89) in the gastric cancer group, with statistically significant difference (p<0.01). In patients treated with anti-HP drugs had the HP infection rate effectively reduced. The treatment effective rates of patients with BRG and gastric cancer complicated with HP infection after eradication of HP were 82.8 and 68.8%, respectively, while those of patients with non-eradicated HP were only 46.4 and 37.5 %, respectively. The differences between the two groups were statistically significant (p<0.05). CONCLUSION: HP is directly and closely related to the occurrence of gastric diseases, HP infection rate in patients with gastric cancer is significantly higher than that in patients with BRG, and the treatment of HP can effectively improve the rehabilitation rate in patients with gastric diseases.

PPARγ Antagonizes Hypoxia-Induced Activation of Hepatic Stellate Cell through Cross Mediating PI3K/AKT and cGMP/PKG Signaling.

BACKGROUND AND AIMS: Accumulating evidence reveals that PPARγ plays a unique role in the regulation of hepatic fibrosis and hepatic stellate cells (HSCs) activation. This study was aimed at investigating the role of PPARγ in hypoxia-induced hepatic fibrogenesis and its possible mechanism. METHODS: Rats used for CCl4-induced hepatic fibrosis model were exposed to hypoxia for 8 hours each day. Rats exposed to hypoxia were treated with or without the PPARγ agonist rosiglitazone. Liver sections were stained with HE and Sirius red staining 8 weeks later. HSCs were exposed to hypoxic environment in the presence or absence of rosiglitazone, and expression of PPARγ and two fibrosis markers, α-SMA and desmin, were measured using western blot and immunofluorescence staining. Next, levels of PPARγ, α-SMA, and desmin as well as PKG and cGMP activity were detected using PI3K/AKT and a cGMP activator or inhibitor. RESULTS: Hypoxia promoted the induction and progress of hepatic fibrosis and HSCs activation. Meanwhile, rosiglitazone significantly antagonized the effects induced by hypoxia. Signaling by sGC/cGMP/PKG promoted the inhibitory effect of PPARγ on hypoxia-induced activation of HSCs. Moreover, PI3K/AKT signaling or PDE5 blocked the above response of PPARγ. CONCLUSION: sGC/cGMP/PKG and PI3K/AKT signals act on PPARγ synergistically to attenuate hypoxia-induced HSC activation.

Immune checkpoint molecule PD-1 acts as a novel biomarker for the pathological process of gestational diabetes mellitus.

AIM: Accumulating evidence suggested that challenge of the maternal-fetal interaction during pregnancy might cause the impairment of immunological hemostasis and lead to gestational diabetes mellitus (GDM) pathological process. Immune checkpoint molecule PD-1 is one of the critical molecule balancing immune response and immunological tolerance. METHODS: PD-1 expressions on T-cell subsets of GDM patients and control groups were measured via flow cytometric analysis and followed up. RESULTS: Downregulation of PD-1 acted as an indicator for GDM occurrence in the third trimester of pregnancy. With the recovery of GDM, PD-1 expression restored to normal level. CONCLUSION: PD-1 expression on T-cell subsets is a novel biomarker for the occurrence and recovery of GDM.

Curcumin inhibits gastric cancer-derived mesenchymal stem cells mediated angiogenesis by regulating NF-κB/VEGF signaling.

Cancer-derived mesenchymal stem cells (MSCs) seem to play an important role in mediating tumor angiogenesis. Recently, curcumin has been shown to display multiple therapeutic properties, including anticancer activity. In the present study, we have tried to explore the role of curcumin in regulating gastric cancer cells-derived mesenchymal stem cells (GC-MSCs) mediated angiogenesis. Our results showed that curcumin attenuated the high expression levels of fibroblast proteins (α-SMA & Vimentin) in GC-MSCs. Its treatment also inhibited GC-MSCs induced human umbilical vein endothelial cells (HUVEC) tube formation, migration and colony formation. Furthermore, it was noticed that curcumin abrogated NF-κB signaling activity and VEGF production in GC-MSCs. Next, to establish the link between regulation of NF-κB/VEGF signaling by curcumin, and its influence on GC-MSC-derived angiogenesis, we pretreated GC-MSCs with either NF-κB inhibitor PDTC or a neutralizing antibody against VEGF (NA-VEGF), and then collected conditioned media (CM). The HUVEC cells were then cultured in this conditioned media to test their ability to form tubes, migrate and form colonies. Our results demonstrated that NF-κB/VEGF signaling is important for GC-MSCs induced tube formation, migration and colony formation in HUVEC cells. Moreover, we also observed that NF-κB/VEGF signaling regulated VEGF expression of gastric cancer cells both in vitro and in vivo. Overall, our study indicated that curcumin may serve as a novel therapeutic target for GC-MSCs derived angiogenesis, by inhibiting NF-κB/VEGF signaling.

Comparative analysis of the interaction of HSPs in dendritic cells, macrophages, RGM-1 cells infected by Helicobacter pylori.

Helicobacter pylori may cause chronic gastritis, even gastric cancer, however, antigen-presenting cells (APCs) are most important immune cells involved in the induction and expression of the underlying inflammatory responses to resist H. pylori. To study the interaction of HSPs in dendritic cells (DCs), macrophages and RGM-1 cells infected with H. pylori, HSP-27, HSP-60, HSP-70 and HSP-90 proteins were analyzed in the mucosa tissue or serum of gastritis patients caused by H. pylori, and in cell supernatant of DCs, macrophages, RGM-1 infected by H. pylori, or in above host cells. We found that HSP-27, HSP-60, HSP-70 and HSP-90 decreased in gastric epithelial cells, but increased significantly in DCs, macrophages. Meanwhile, inflammation associated proteins iNOS-2 and COX-2 were participated in the expression of HSPs in the process of host cells defensing against H. pylori infection. These findings contribute to understand the functions of HSP-27, HSP-60, HSP-70 and HSP-90 in H. pylori infection APCs and gastric epithelial cells indicating that HSPs would be diagnostic markers for H. pylori infection.