Forced Expression of CXCL10 Prevents Liver Metastasis of Colon Carcinoma Cells by the Recruitment of Natural Killer Cells

Kikuchi, Norihito; Ye, Jiabin; Hirakawa, Jotaro; Kawashima, Hiroto

doi:10.1248/bpb.b18-00538

Cited by 20 publications

(12 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We found that ACE2 and DPP4 were highly expressed and significantly correlated to the innate and adaptive immunity-related cells, as well as IL-10, IL-6, CXCL10, CCL2-CCL5, TGFB1 in KIRC tumors only. Upregulation of CXCL10 can enhance the levels of Tumor-infiltrating CD8+ T cell and natural killer cells (Humblin and Kamphorst, 2019 ; Kikuchi et al, 2019 ; Petty et al, 2019 ). T regulatory cells and macrophages get recruited by CCL5 (Wang et al, 2017 ; Walens et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Renal Carcinoma Is Associated With Increased Risk of Coronavirus Infections

Tripathi

Deshmukh

Creighton

et al. 2020

Front. Mol. Biosci.

View full text Add to dashboard Cite

Background: The current COVID-19 pandemic has affected most severely people with old age, or with comorbidities like hypertension, diabetes mellitus, and cancer. Cancer patients are twice more likely to contract the disease because of the malignancy or treatment-related immunosuppression; hence identification of the vulnerable population among these patients is essential.Method: We took a bioinformatics approach to analyze the gene and protein expression data of these coronavirus receptors (DPP4, ANPEP, ENPEP, TMPRSS2) in human normal and cancer tissues of multiple organs including the brain, liver, kidney, heart, lung, skin, GI tract, pancreas, endocrine tissues, and the reproductive organs. RNA-Seq data from The Cancer Genome Atlas (TCGA) and GTeX databases were used for extensive profiling analysis of these receptors across 9,736 tumors and 8,587 normal tissues comparing coronavirus receptors. Protein expression from immunohistochemistry data was assessed from The Human Protein Atlas database including 144 samples, corresponding to 48 different normal human tissue types, and 432 tumor samples from 216 different cancer patients. The correlations between immune cell infiltration, chemokine, and cytokines were investigated via Tumor Immune Estimation Resource (TIMER) and TCGA.Result: We found that among all, renal tumor and normal tissues exhibited increased levels of ACE2, DPP4, ANPEP, and ENPEP. Our results revealed that TMPRSS2 may not be the co-receptor for coronavirus infection in renal carcinoma patients. The other receptors DPP4, ANPEP, and ENPEP may act as the compensatory receptor proteins to help ACE2. The receptors' expression levels were variable in different tumor stage, molecular, and immune subtypes of renal carcinoma. Intriguingly, in clear cell renal cell carcinomas, coronavirus receptors were associated with high immune infiltration, markers of immunosuppression, and T cell exhaustion.Conclusion: Our study indicates that CoV receptors may play an important role in modulating the immune infiltrate and hence cellular immunity in renal carcinoma. As our current knowledge of pathogenic mechanisms will improve, it may help us in designing focused therapeutic approaches.

show abstract

Section: Discussionmentioning

confidence: 99%

Renal Carcinoma Is Associated With Increased Risk of Coronavirus Infections

Tripathi

Deshmukh

Creighton

et al. 2020

Front. Mol. Biosci.

View full text Add to dashboard Cite

show abstract

“…CXCL10 is a selective ligand for CXCR3, and the CXCL10/CXCR3 signaling pathway regulates leukocyte trafficking and angiogenesis through paracrine interactions, while signaling of autocrine CXCL10/CXCR3 in tumor cells can promote growth of cancer and metastasis by regulating cell adhesion, invasion, and migration capabilities ( 34 , 35 ). There are also studies associating the CXCL10/CXCR3 gene expression pathway with enhanced metastatic potential and poor prognosis in patients with melanoma ( 36 ) and colon cancer ( 37 ). Polimeno et al.…”

Section: Discussionmentioning

confidence: 99%

Identification of CXCL10 as a Prognostic Biomarker for Clear Cell Renal Cell Carcinoma

Wang

Yan

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

BackgroundOne of the widespread forms of kidney tumor is clear cell renal cell carcinoma (ccRCC), with poor prognosis and insensitivity to radio chemotherapy as there is limited capacity to understand the disease mechanism. This study aims at identifying potential biomarkers and the underlying processes of ccRCC using bioinformatics analysis.MethodsTranscriptome data of relevant samples were downloaded from The Cancer Genome Atlas (TCGA) database. R software was used to screen differentially expressed genes (DEGs) using the “edgeR” package. Two types of analysis—Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment—were accomplished by applying Database for Annotation, Visualization, and Integrated Discovery (DAVID) and Search Tool for the Retrieval of Interacting Genes database (STRING) online bioinformatics tools. A protein–protein interaction (PPI) network of the identified DEGs was constructed using Cytoscape software, and hub genes were subsequently selected via the Cytohubba plug-in. The selected genes were input into Oncomine for verification. Finally, selected hub genes were analyzed by doing survival analysis to notice the relationship between survival (OS) rate and the selected genes’ level of expression.ResultsThere were 1,855 DEGs found connected to ccRCC, with 1,207 upregulated genes and 648 downregulated genes. G-protein-coupled receptor signaling pathway, integral component of membrane, calcium ion binding, and cytokine–cytokine receptor interaction were among the DEGs discovered. Oncomine confirmed the top six hub genes from the PPI network (C3, CXCR3, CXCL10, CCR5, CCL4, and CCL5). A high level of expression of CXCL10, one of these hub genes, was linked to a poor prognosis in individuals with ccRCC. The results of survival analysis showed that the expression level of CXCL10 was significantly correlated with the prognosis of ccRCC patients (p < 0.05).ConclusionsFrom the analysis, the following results were drawn: CXCL10 might be a potential prognostic biomarker and novel therapeutic target for ccRCC.

show abstract

“…In most studies, in order to establish pulmonary and liver metastases, CT-26 cells have been injected in the tail vein of the mice (37,38). Moreover, in one study for establishing metastatic liver tumors, CT-26 cells have been injected into the spleen (39). In our model, unlike the above-mentioned studies, the aim of the study was not solely to investigate the effect of TEXomiR on metastases.…”

Section: Discussionmentioning

confidence: 99%

Tumor-Derived Exosomes Enriched by miRNA-124 Promote Anti-tumor Immune Response in CT-26 Tumor-Bearing Mice

et al. 2021

View full text Add to dashboard Cite

Exosomes have been introduced as a new alternative delivery system for the transmission of small molecules. Tumor-derived exosomes (TEXs) not only contain tumor-associated antigens to stimulate antitumor immune responses but also act as natural carriers of microRNAs. The aim of the current study was to evaluate the efficacy of miR-124-3p-enriched TEX (TEXomiR) as cell-free vaccine in the induction of antitumor immune responses in a mouse model of colorectal cancer. Briefly, the exosomes were isolated from cultured CT-26 cell line, and modified calcium chloride method was used to deliver miR-124-3p mimic into the exosomes. We used a CT-26-induced BALB/c mouse model of colorectal cancer and analyzed the effect of TEXomiR on survival, tumor size, spleen and tumor-infiltrated lymphocytes, and splenocyte proliferation. Furthermore, intra-tumor regulatory T cells, cytotoxic activity of the splenocytes, and cytokine secretion was also evaluated to describe the anti-tumor immune response. When the tumor size reached 100 mm3, the mice were injected with TEXomiR, TEX, and/or phosphate-buffered saline (PBS) subcutaneously three times with 3-day interval, and then tumor size was monitored every 2 days. The in vitro results indicated that TEXs could efficiently deliver functional miR-124-3p mimic. The in vivo evaluation in tumor-bearing mice showed that treatment with TEXomiR can elicit a stronger anti-tumor immune response than unloaded TEX and PBS. Significant tumor growth inhibition and increased median survival time was achieved in tumor-bearing mice treated with TEXomiR. A significant decrease in CD4/CD8 and Treg/CD8 ratio in tumor tissue was demonstrated. Moreover, increased cytotoxicity and proliferation of splenocytes in the TEXomiR group compared to the TEX and PBS groups were identified. Taken together, our data demonstrated that tumor-derived exosomes efficiently deliver miR-124-3p mimic, and TEXomiR promotes anti-tumor immune responses.

show abstract

Forced Expression of CXCL10 Prevents Liver Metastasis of Colon Carcinoma Cells by the Recruitment of Natural Killer Cells

Cited by 20 publications

References 35 publications

Renal Carcinoma Is Associated With Increased Risk of Coronavirus Infections

Renal Carcinoma Is Associated With Increased Risk of Coronavirus Infections

Identification of CXCL10 as a Prognostic Biomarker for Clear Cell Renal Cell Carcinoma

Tumor-Derived Exosomes Enriched by miRNA-124 Promote Anti-tumor Immune Response in CT-26 Tumor-Bearing Mice

Contact Info

Product

Resources

About