Extracellular Vesicles and Hepatocellular Carcinoma: Opportunities and Challenges

Wang, Juan; Wang, Xiaoya; Zhang, Xintong; Shao, Tingting; Luo, Yanmei; Wang, Wei; Han, Yunwei

doi:10.3389/fonc.2022.884369

Cited by 14 publications

(15 citation statements)

References 298 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is interesting to note that HCC-derived exosomes can regulate immune cells during the progression of tumors 8,9 . Another study has verified that HCC cells–secreted EVs produce direct immune effects to stimulate target cells, contributing to the invasion of HCC 10 . Moreover, bioinformatics analysis in the current study revealed that lysyl oxidase like-4 (LOXL4) was differentially expressed in HCC.…”

mentioning

confidence: 54%

“…8,9 Another study has verified that HCC cellssecreted EVs produce direct immune effects to stimulate target cells, contributing to the invasion of HCC. 10 Moreover, bioinformatics analysis in the current study revealed that lysyl oxidase like-4 (LOXL4) was differentially expressed in HCC. Emerging evidence has proved the roles of LOXL4 in tumor cell growth and metastasis, including HCC.…”

mentioning

confidence: 71%

See 1 more Smart Citation

LOXL4 Shuttled by Tumor Cells–derived Extracellular Vesicles Promotes Immune Escape in Hepatocellular Carcinoma by Activating the STAT1/PD-L1 Axis

Zhao,

Pei,

Ding

et al. 2023

Journal of Immunotherapy

View full text Add to dashboard Cite

Emerging evidence has validated that extracellular vesicles (EVs) regulate hepatocellular carcinoma (HCC) progression, while its role in HCC immune escape remains to be elucidated. This study investigates the role of EVs-encapsulated lysyl oxidase like-4 (LOXL4) derived from tumor cells in HCC immune escape. HCC-related microarray data sets GSE36376 and GSE87630 were obtained for differential analysis, followed by identifying the essential genes related to the prognosis of HCC patients. Bone marrow–derived macrophages were treated with EVs derived from mouse Hepa 1–6 cells and cocultured with CD8+T cells to observe the CD8+T-cell activity. At last, a mouse HCC orthotopic xenograft model was constructed to verify the effects of HCC cell-derived EVs on the immune escape of HCC cells and tumorigenicity in vivo by delivering LOXL4. It was found that ACAT1, C4BPA, EHHADH, and LOXL4 may be the essential genes related to the prognosis of HCC patients. On the basis of the TIMER database, there was a close correlation between LOXL4 and macrophage infiltration in HCC. Besides, STAT1 was closely related to LOXL4. In vitro experiments demonstrated that LOXL4 could induce programmed death-ligand 1 expression in macrophages and immunosuppression by activating STAT1. In vivo experiments also verified that HCC cell-derived EVs promoted the immune escape of HCC cells and tumorigenicity by delivering LOXL4. LOXL4 was delivered into macrophages via EVs to induce programmed death-ligand 1 by activating STAT1 and inhibiting the killing ability of CD8+T cells to HCC cells, thus promoting immune escape in HCC.

show abstract

mentioning

confidence: 54%

mentioning

confidence: 71%

LOXL4 Shuttled by Tumor Cells–derived Extracellular Vesicles Promotes Immune Escape in Hepatocellular Carcinoma by Activating the STAT1/PD-L1 Axis

Zhao,

Pei,

Ding

et al. 2023

Journal of Immunotherapy

View full text Add to dashboard Cite

show abstract

“…Recently, surface markers of EVs have gained attention since they indicated presence of HCC and cholangiocarcinoma with increased levels of CD147 and CD133 [13]. Additionally, EVs transfer proteins and different types of RNAs, including miRNAs, from highly malignant cells to surrounding cells, promoting HCC migratory and metastatic capacities [14]. This is of particular interest because tumor invasion lead to early recurrence of HCC after resection, resulting in high recurrence rates [15].…”

Section: Discussionmentioning

confidence: 99%

Extracellular vesicles as potential biomarkers for diagnosis and recurrence detection of hepatocellular carcinoma: A pilot study

Juratli

Roushansarai

Oppermann

et al. 2023

Preprint

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor and a leading cause of cancer-related deaths worldwide. However, current diagnostic tools are often invasive and technically limited. Extracellular vesicles (EVs), which play vital roles in HCC growth and metastasis, serving as potential novel biomarkers. Molecular analysis of peripherally EVs could be revolutionary for early tumor diagnosis and detecting tumor recurrence. A prospective single-center cohort study including 37 HCC patients and 20 patients with non-malignant liver disease (NMLD), as a control group, was conducted. Peripherally EVs of both groups were analyzed before and after liver surgery. The study utilized microbead-based magnetic particle sorting and flow cytometry to detect 37 characteristic surface proteins of EVs. Furthermore, HCC patients who experienced tumor recurrence (R-HCC) within 12 months after surgery were compared to HCC patients without recurrence (NR-HCC). R-HCC patients (n = 12/20) showed significantly lower levels of CD31 compared to NR-HCC patients (p = 0.0033). The NMLD-group showed significantly higher expressions of CD41b than the HCC group (p = 0.0286). The study determined significant short-term changes in CD19 dynamics in the NMLD-group, with preoperative values being significantly higher than postoperative values (p = 0.0065). This finding of our pilot study suggests EVs as potential targets for the development of diagnostic and therapeutic approaches for the early and non-invasive detection of HCC recurrence by monitoring the dynamics of specific EVs markers, such as CD41b and CD31, in HCC patients. Overall, the potential of EVs as diagnostic and therapeutic targets for HCC recurrence represents a promising area of research that could have a significant impact on the management of this disease in the future.

show abstract

“…[14][15][16] Secretion of exosomes is a pivotal way for BMSC to exert effects on cancer progerssion. 17,18 Accumulating evidence showed that exosomes released from BMSCs regulate tumor progression by packaging some specific miRNAs. [19][20][21] But limited studies focused on the effect of BMSC-derived exosomes exerting on HCC metastasis via transmitting specific miRNAs.…”

Section: Introductionmentioning

confidence: 99%

“…BMSCs are multipotent cells which function in different human pathological processes, including cancer development 14–16 . Secretion of exosomes is a pivotal way for BMSC to exert effects on cancer progerssion 17,18 . Accumulating evidence showed that exosomes released from BMSCs regulate tumor progression by packaging some specific miRNAs 19–21 .…”

Section: Introductionmentioning

confidence: 99%

Exosomal miR‐374c‐5p derived from mesenchymal stem cells suppresses epithelial‐mesenchymal transition of hepatocellular carcinoma via the LIMK1‐Wnt/β‐catenin axis

Ding

Lou

Fan

et al. 2023

Environmental Toxicology

View full text Add to dashboard Cite

Metastasis is a leading cause to treatment failure in hepatocellular carcinoma (HCC) patients. Exosomes act as pivotal mediators in communication between different cells and exert effects on recipient cells by delivering bioactive cargoes, such as microRNAs (miRNAs). MiRNAs function in multiple steps of HCC development, including metastasis. MiR-374c-5p was previously identified as a tumor suppressor in some malignancies, while the current knowledge of its role in HCC metastasis is still limited. Herein, miR-374c-5p was found to be downregulated in HCC cell lines and clinical samples, and positively related with favorable prognosis in HCC patients.MiR-374c-5p transferred by exosomes derived from bone marrow mesenchymal stem cell (BMSC) suppressed migration, invasion and proliferation of HCC cells.LIMK1 was verified as downstream target gene of miR-374c-5p. Knockdown of LIMK1 reduced invasion, migration and proliferation of HCC cells, whereas overexpression functioned oppositely. The miR-374c-5p/LIMK1 axis suppressed epithelialmesenchymal transition (EMT) by inactivating Wnt/β-catenin pathway. In addition, miR-374c-5p was downregulated and LIMK1 upregulated in TGF-β1 induced EMT.This EMT model could be reversed by LIMK1 silencing or miR-374c-5p overexpression. These results suggest that exo-miR-374c-5p suppresses EMT via targeting LIMK1-Wnt/β-catenin axis and the axis is involved in TGF-β1 induced metastasis of HCC, thereby identifying miR-374c-5p as a potential target for HCC treatment.

show abstract

Extracellular Vesicles and Hepatocellular Carcinoma: Opportunities and Challenges

Cited by 14 publications

References 298 publications

LOXL4 Shuttled by Tumor Cells–derived Extracellular Vesicles Promotes Immune Escape in Hepatocellular Carcinoma by Activating the STAT1/PD-L1 Axis

LOXL4 Shuttled by Tumor Cells–derived Extracellular Vesicles Promotes Immune Escape in Hepatocellular Carcinoma by Activating the STAT1/PD-L1 Axis

Extracellular vesicles as potential biomarkers for diagnosis and recurrence detection of hepatocellular carcinoma: A pilot study

Exosomal miR‐374c‐5p derived from mesenchymal stem cells suppresses epithelial‐mesenchymal transition of hepatocellular carcinoma via the LIMK1‐Wnt/β‐catenin axis

Contact Info

Product

Resources

About