Macrophage polarization and meta-inflammation

Translational research, Journal Year: 2017, Volume and Issue: 191, P. 29 - 44

Published: Nov. 4, 2017

Language: Английский

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Loss of exosomal miR-320a from cancer-associated fibroblasts contributes to HCC proliferation and metastasis

Cancer Letters, Journal Year: 2017, Volume and Issue: 397, P. 33 - 42

Published: March 10, 2017

Language: Английский

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Exosome-mediated communication in the tumor microenvironment contributes to hepatocellular carcinoma development and progression

Journal of Hematology & Oncology, Journal Year: 2019, Volume and Issue: 12(1)

Published: May 29, 2019

The tumor microenvironment (TME) is an essential intrinsic portion of hepatocellular carcinoma (HCC) for the regulation its origination, development, invasion, and metastasis. As emerging components tumor-host interaction, exosomes are increasingly recognized as professional carriers information in TME pivotal molecular entities involved tumorigenic setup. However, much remains unknown about role exosome communication system within development progression HCC. In this review, we focus on roles probable mechanisms HCC show exosome-based immune to promote Multiple processes HCC, including survival, growth, angiogenesis, We also discuss specific by molding hospitable such providing energy, transmitting protumor signals, evading inhibitory signals. addition, induce angiogenesis changing biological characteristics endothelial cells directly regulating proangiogenic propermeability factors. Furthermore, may lead metastatic invasion epithelial-mesenchymal transformation, extracellular matrix degradation, vascular leakage. Finally, summarize therapeutic usage attempt provide a theoretical reference modern antitumor agents designed target these mechanisms.

Language: Английский

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Tumor‐associated macrophages in liver cancer: From mechanisms to therapy

Cancer Communications, Journal Year: 2022, Volume and Issue: 42(11), P. 1112 - 1140

Published: Sept. 7, 2022

Abstract Multidimensional analyses have demonstrated the presence of a unique tumor microenvironment (TME) in liver cancer. Tumor‐associated macrophages (TAMs) are among most abundant immune cells infiltrating TME and present at all stages cancer progression, targeting TAMs has become one favored immunotherapy strategies. In addition, distinct origins. At early stage cancer, can provide niche for maintenance stem cells. contrast, (CSCs) or poorly differentiated key factors modulating macrophage activation. review, we first propose origin connection between precursor Macrophages undergo dynamic phenotypic transition during carcinogenesis. this course such transition, it is critical to determine appropriate timing therapy block specific markers suppress pro‐tumoral TAMs. The review provides more detailed discussion trends surface than previous reviews. Complex crosstalk occurs play indispensable roles angiogenesis, autophagy due their heterogeneity robust plasticity. interact with other by directing cell‐to‐cell contact secreting various effector molecules. Similarly, combined drive recruitment polarization. Despite latest achievements advancements treatment strategies following studies, comprehensive discussions on communication currently lacking. discussed interactions (from cell maturation), therapeutic (including chimeric antigen receptor macrophages), clinical trials hepatocellular carcinoma (HCC) intrahepatic cholangiocarcinoma (iCCA) rationale further investigation as potential target treating patients

Language: Английский

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The role of exosomal noncoding RNAs in cancer

Molecular Cancer, Journal Year: 2019, Volume and Issue: 18(1)

Published: March 9, 2019

Extracellular vesicles (EVs) membranes enclose nanosized with a size range of 30-150 nm and are plentiful in our body both physiological pathological conditions. Exosomes, type EV, important mediators intracellular communication among tumor cells, immune stromal cells. They can shuttle bioactive molecules, such as proteins, lipids, RNA, DNA; however, the precise function EVs remains largely unknown. In recent years, tumor-associated cargo exosomes has been hot topic research, especially respect to noncoding RNAs (ncRNAs). Herein, we review role exosomal ncRNAs, including miRNAs long RNAs, biological processes. Clinically, ncRNAs may eventually become novel biomarkers therapeutic targets cancer progression.

Language: Английский

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Role of exosomal non-coding RNAs from tumor cells and tumor-associated macrophages in the tumor microenvironment

Molecular Therapy, Journal Year: 2022, Volume and Issue: 30(10), P. 3133 - 3154

Published: April 9, 2022

Exosomes have a crucial role in intercellular communication and mediate interactions between tumor cells tumor-associated macrophages (TAMs). Exosome-encapsulated non-coding RNAs (ncRNAs) are involved various physiological processes. Tumor-derived exosomal ncRNAs induce M2 macrophage polarization through signaling pathway activation, signal transduction, transcriptional post-transcriptional regulation. Conversely, TAM-derived promote proliferation, metastasis, angiogenesis, chemoresistance, immunosuppression. MicroRNAs gene silencing by directly targeting mRNAs, whereas lncRNAs circRNAs act as miRNA sponges to indirectly regulate protein expressions. The of tumor-host is ubiquitous. Current research increasingly focused on the microenvironment. On basis "cancer-immunity cycle" hypothesis, we discuss effects immune T cell exhaustion, overexpression programmed death ligands, create immunosuppressive Furthermore, potential applications prospects clinical biomarkers drug delivery systems. 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Language: Английский

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Hepatocellular Carcinoma Cell-Secreted Exosomal MicroRNA-210 Promotes Angiogenesis In Vitro and In Vivo

Molecular Therapy — Nucleic Acids, Journal Year: 2018, Volume and Issue: 11, P. 243 - 252

Published: March 6, 2018

We previously found that 19 microRNAs (miRNAs) significantly increased in the sera of hepatocellular carcinoma (HCC) patients. Here, we evaluated whether these miRNAs were secreted by HCC cells and contributed to tumor angiogenesis. High level miR-210-3p (miR-210) was detected exosomes isolated from patients conditioned media hepatoma cells. Higher miR-210 serum correlated with higher microvessel density tissues. Moreover, cell-secreted promoted vitro tubulogenesis endothelial cells, which strengthened overexpressing but attenuated repressing or DROSHA This pro-tubulogenesis effect also abrogated antagonizing Subsequent vivo studies revealed Matrigel plug subcutaneous xenografts treated cell-derived exosomal displayed much more vessels. Furthermore, could be delivered into directly inhibited expression SMAD4 STAT6, resulting enhanced Collectively, may transferred thereby promotes angiogenesis targeting STAT6. Our findings identify a novel mechanism highlight biological importance miR-210.

Language: Английский

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MicroRNA regulons in tumor microenvironment

Oncogene, Journal Year: 2014, Volume and Issue: 34(24), P. 3085 - 3094

Published: Aug. 18, 2014

Cancer initiation and progression are defined by the behavior of cancer cells per se development tumor tissues, both which modulated crosstalk between surrounding microenvironment. Advances in research have highlighted significance constant evolution microenvironment, leading to formation, metastasis refractoriness therapy. MicroRNAs (miRNAs) small non-coding RNAs that function as major players posttranscriptional gene regulation diverse biological processes. They suppressors promoters many aspects autonomous cells. Theoretically, dysfunction regulatory networks is one driving forces for alterations ostensibly normal In this context, core targets miRNAs, termed miRNA regulons, currently being expanded include various modulators Recent advances two important roles played miRNAs microenvironments: transform microenvironment via non-cell-autonomous mechanisms, neighboring stabilize hallmark traits. These observations epitomize distal proximal functions microenvironments, respectively. Such affects angiogenesis, immune invasion tumor–stromal interactions. This review summarizes recent findings on mechanisms miRNA-mediated with a perspective design therapeutic interventions.

Language: Английский

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TGFβ Triggers miR-143/145 Transfer From Smooth Muscle Cells to Endothelial Cells, Thereby Modulating Vessel Stabilization

Circulation Research, Journal Year: 2015, Volume and Issue: 116(11), P. 1753 - 1764

Published: March 24, 2015

Rationale: The miR-143/145 cluster is highly expressed in smooth muscle cells (SMCs), where it regulates phenotypic switch and vascular homeostasis. Whether plays a role neighboring endothelial (ECs) still unknown. Objective: To determine whether SMCs control EC functions through passage of miR-143 miR-145. Methods Results: We used cocultures ECs under different conditions, as well intact vessels to assess the transfer miR-145 from one cell type another. Imaging cocultured transduced with fluorescent miRNAs suggested that miRNA involves membrane protrusions known tunneling nanotubes. Furthermore, we show modulated by transforming growth factor (TGF) β pathway because both specific factor-β (TGFβ) inhibitor (SB431542) an shRNA against TGFβRII suppressed ECs. Moreover, angiogenesis reducing proliferation index their capacity form vessel-like structures when cultured on matrigel. also identified hexokinase II ( HKII ) integrin 8 ITGβ8 )—2 genes essential for angiogenic potential ECs—as targets miR-145, respectively. inhibition these phenotype, similarly overexpression These findings were confirmed ex vivo approaches, which was shown TGFβ vessel stress, respectively, triggered Conclusions: Our results demonstrate act communication molecules between modulate stabilization properties

Language: Английский

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MicroRNAs as mediators and communicators between cancer cells and the tumor microenvironment

Oncogene, Journal Year: 2015, Volume and Issue: 34(48), P. 5857 - 5868

Published: April 13, 2015

Language: Английский

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