bims-exocan 2024-06-09 papers

bims-exocan

Biomed News

on Exosomes roles in cancer

Issue of 2024–06–09
nine papers selected by
Muhammad Rizwan, COMSATS University

The involvement and application potential of exosomes in breast cancer immunotherapy.
Exosomal lncRNA SNHG12 promotes angiogenesis and breast cancer progression.
Colorectal cancer cells with high metastatic potential drive metastasis by transmitting exosomal miR-20a-3p through modulating NF1/MAPK pathway.
The microRNA Let-7 and its exosomal form: Epigenetic regulators of gynecological cancers.
Exploring the clinical transition of engineered exosomes designed for intracellular delivery of therapeutic proteins.
Exosomal circPVT1 promotes angiogenesis in laryngeal cancer by activating the Rap1b-VEGFR2 signaling pathway.
Exosome-based anticancer vaccines: From Bench to Bedside.
Exosome-Mediated Communication in Thyroid Cancer: Implications for Prognosis and Therapeutic Targets.
Exosomal circSIPA1L3-mediated intercellular communication contributes to glucose metabolic reprogramming and progression of triple negative breast cancer.

Front Immunol. 2024 ;15 1384946

The involvement and application potential of exosomes in breast cancer immunotherapy.

Yun Wang, Qiji Ma, Tielin Wang, Jie Xing, Qirong Li, Dongxu Wang, Gang Wang.

  Breast cancer has a high incidence and a heightened propensity for metastasis. The absence of precise targets for effective intervention makes it imperative to devise enhanced treatment strategies. Exosomes, characterized by a lipid bilayer and ranging in size from 30 to 150 nm, can be actively released by various cells, including those in tumors. Exosomes derived from distinct subsets of immune cells have been shown to modulate the immune microenvironment within tumors and influence breast cancer progression. In addition, tumor-derived exosomes have been shown to contribute to breast cancer development and progression and may become a new target for breast cancer immunotherapy. Tumor immunotherapy has become an option for managing tumors, and exosomes have become therapeutic vectors that can be used for various pathological conditions. Edited exosomes can be used as nanoscale drug delivery systems for breast cancer therapy, contributing to the remodeling of immunosuppressive tumor microenvironments and influencing the efficacy of immunotherapy. This review discusses the regulatory role of exosomes from different cells in breast cancer and the latest applications of exosomes as nanoscale drug delivery systems and immunotherapeutic agents in breast cancer, showing the development prospects of exosomes in the clinical treatment of breast cancer.

Keywords:  breast cancer; exosomes; immunity; tumor immunotherapy; tumor microenvironment

DOI:  https://doi.org/10.3389/fimmu.2024.1384946
Breast Cancer. 2024 Jun 04.

Exosomal lncRNA SNHG12 promotes angiogenesis and breast cancer progression.

Yan Chen, Yuxin Zhou, Jiafeng Chen, Jiahui Yang, Yijie Yuan, Weizhu Wu.

   OBJECTIVE: Breast cancer is one of the most prevalent malignancies in women. Exosomes are important mediators of intercellular communication; however, their regulatory mechanisms in human umbilical vein endothelial cells (HUVECs) angiogenesis in breast cancer remain unknown.
METHODS: We isolated and characterized breast cancer cell-derived exosomes and investigated their functions. Exosomal sequencing and the TCGA database were used to screen long non-coding RNA (lncRNA). In vitro and in vivo experiments were performed to investigate the role of exosomal lncRNA in HUVEC angiogenesis and tumor growth. Molecular methods were used to demonstrate the molecular mechanism of lncRNA.
RESULTS: We demonstrated that breast cancer cell-derived exosomes promoted HUVEC proliferation, tube formation, and migration. Combining exosomal sequencing results with The Cancer Genome Atlas Breast Cancer database, we screened lncRNA small nucleolar RNA host gene 12 (SNHG12), which was highly expressed in breast cancer cells. SNHG12 was also upregulated in HUVECs co-cultured with exosome-overexpressed SNHG12. Moreover, overexpression of SNHG12 in exosomes increased HUVEC proliferation and migration, whereas deletion of SNHG12 in exosomes showed the opposite effects. In vivo experiments showed that SNHG12 knockdown in exosomes inhibited breast cancer tumor growth. Transcriptome sequencing identified MMP10 as the target gene of SNHG12. Functional experiments revealed that MMP10 overexpression promoted HUVEC angiogenesis. Mechanistically, SNHG12 blocked the interaction between PBRM1 and MMP10 by directly binding to PBRM1. Moreover, exosomal SNHG12 promoted HUVEC angiogenesis via PBRM1 and MMP10.
CONCLUSIONS: In summary, our findings confirmed that exosomal SNHG12 promoted HUVEC angiogenesis via the PBRM1-MMP10 axis, leading to enhanced malignancy of breast cancer. Exosomal SNHG12 may be a novel therapeutic target for breast cancer.

Keywords:  Angiogenesis; Breast cancer; Exosomes; Progression; lncRNA SNHG12

DOI:  https://doi.org/10.1007/s12282-024-01574-6
Carcinogenesis. 2024 Jun 03. pii: bgae036. [Epub ahead of print]

Colorectal cancer cells with high metastatic potential drive metastasis by transmitting exosomal miR-20a-3p through modulating NF1/MAPK pathway.

Yahang Liang, Junyu Li, Tao Li, Mingming Li, Hualin Liao, Yang Liu, Yao Yao, Lingling Yang, Xiong Lei.

  Cancer cells exhibit heterogenous metastatic potential, and high metastatic subclones can enhance metastatic potential of low metastatic subclones by transmitting some factors. Exosomal miRNAs play a pivotal role in the crosstalk of heterogenous metastatic subclones. This study discovered that miR-20a-3p was upregulated in colorectal adenocarcinoma (CRA), correlated with metastasis, and potentially served as a prognostic indicator for CRA. miR-20a-3p could promote the proliferation, migration and invasion of CRA cells. Interestingly, high metastatic CRA cells could promote malignant phenotypes of low metastatic CRA cells by transmitting exosomal miR-20a-3p. Mechanically, miR-20a-3p could inhibit NF1, thereby activate the RAS-mediated mitogen-activated protein kinases (MAPK) signaling pathway to drive the metastasis of CRA. In summary, our study provided the evidence that colorectal cancer cells with high metastatic potential drive metastasis by transmitting exosomal miR-20a-3p through modulating NF1/MAPK pathway.

Keywords:  Colorectal cancer; Exosomes; MAPK signaling pathway; Metastasis; Tumor microenvironment

DOI:  https://doi.org/10.1093/carcin/bgae036
Cell Biol Toxicol. 2024 Jun 05. 40(1): 42

The microRNA Let-7 and its exosomal form: Epigenetic regulators of gynecological cancers.

Fei Wang, Chundi Zhou, Yanping Zhu, Maryam Keshavarzi.

  Many types of gynecological cancer (GC) are often silent until they reach an advanced stage, and are therefore often diagnosed too late for effective treatment. Hence, there is a real need for more efficient diagnosis and treatment for patients with GC. During recent years, researchers have increasingly studied the impact of microRNAs cancer development, leading to a number of applications in detection and treatment. MicroRNAs are a particular group of tiny RNA molecules that regulate regular gene expression by affecting the translation process. The downregulation of numerous miRNAs has been observed in human malignancies. Let-7 is an example of a miRNA that controls cellular processes as well as signaling cascades to affect post-transcriptional gene expression. Recent research supports the hypothesis that enhancing let-7 expression in those cancers where it is downregulated may be a potential treatment option. Exosomes are tiny vesicles that move through body fluids and can include components like miRNAs (including let-7) that are important for communication between cells. Studies proved that exosomes are able to enhance tumor growth, angiogenesis, chemoresistance, metastasis, and immune evasion, thus suggesting their importance in GC management.

Keywords:  Cervical cancer; Endometrial cancer; Gyncological cancer; Let-7; MicroRNA; Ovarian cancer

DOI:  https://doi.org/10.1007/s10565-024-09884-3
Stem Cells Transl Med. 2024 Jun 05. pii: szae027. [Epub ahead of print]

Exploring the clinical transition of engineered exosomes designed for intracellular delivery of therapeutic proteins.

Minseong Kim, Hojun Choi, Deok-Jin Jang, Hye-Jung Kim, Yujin Sub, Heon Yung Gee, Chulhee Choi.

  Extracellular vesicles, particularly exosomes, have emerged as promising drug delivery systems owing to their unique advantages, such as biocompatibility, immune tolerability, and target specificity. Various engineering strategies have been implemented to harness these innate qualities, with a focus on enhancing the pharmacokinetic and pharmacodynamic properties of exosomes via payload loading and surface engineering for active targeting. This concise review outlines the challenges in the development of exosomes as drug carriers and offers insights into strategies for their effective clinical translation. We also highlight preclinical studies that have successfully employed anti-inflammatory exosomes and suggest future directions for exosome therapeutics. These advancements underscore the potential for integrating exosome-based therapies into clinical practice, heralding promise for future medical interventions.

Keywords:  drug delivery system; exosome purification; exosomes; extracellular vesicles; inflammation; protein therapeutics

DOI:  https://doi.org/10.1093/stcltm/szae027
Carcinogenesis. 2024 Jun 02. pii: bgae030. [Epub ahead of print]

Exosomal circPVT1 promotes angiogenesis in laryngeal cancer by activating the Rap1b-VEGFR2 signaling pathway.

Kexing Lyu, Bingjie Tang, Bixue Huang, Zhenglin Xu, Tesi Liu, Ruihua Fang, Yun Li, Yi Chen, Lin Chen, Minjuan Zhang, Lifan Chen, Wenbin Lei.

  Laryngeal cancer (LC) is the second most common head and neck cancer and has a decreasing 5-year survival rate worldwide. Circular RNAs regulate cancer development in diverse ways based on their distinct biogenesis mechanisms and expansive regulatory roles. However, currently, there is little research on how exosomal circular RNAs are involved in the development of laryngeal cancer. Here, we demonstrated that circPVT1, a circular RNA derived from the well-studied long noncoding RNA PVT1, is correlated with disease progression in LC and promotes angiogenesis both in vivo and in vitro. Mechanistically, circPVT1 is loaded into LC cell-secreted exosomes and taken up by vascular epithelium cells. By sponging miR-30c-5p, exosomal circPVT1 promotes Rap1b expression, which dramatically enhances VEGFR2 and PI3K/AKT pathway activation, ultimately resulting in the induction of angiogenesis. Furthermore, our xenograft models demonstrated that the combination of shRNA-circPVT1 and cetuximab showed high efficacy in inhibiting tumor growth and angiogenesis. Collectively, these findings uncover a novel mechanism of exosomal circular RNA-mediated angiogenesis modulation and provide a preclinical rationale for testing this analogous combination in patients with LC.

Keywords:  Angiogenesis; Exosomal circPVT1; Laryngeal cancer; Rap1b; VEGFR2

DOI:  https://doi.org/10.1093/carcin/bgae030
Cancer Lett. 2024 May 31. pii: S0304-3835(24)00383-5. [Epub ahead of print] 216989

Exosome-based anticancer vaccines: From Bench to Bedside.

Guo Zhao, Yuning Wang, Shujun Xing, Yale Jiang, Jiatong Ding, Yuanting Cai, Peiwen Ma, Huilei Miao, Yuan Fang, Ning Jiang, Dandan Cui, Yue Yu, Qiyu Tang, Shuhang Wang, Ning Li.

  Exosomes, a subset of extracellular vesicles, are released by all active cells and play a crucial role in intercellular communications. Exosomes could facilitate the transfer of various biologically active molecules, such as DNA, non-coding RNAs, and proteins, from donor to recipient cells, thereby participating in diverse biological and pathological processes. Besides, exosomes possess unique characteristics, including non-toxicity, low-immunogenicity, and stability within biological systems, rendering them highly advantageous for cancer drug development. Meanwhile, accumulating evidence suggests that exosomes originating from tumor cells and immune cells possess distinct composition profiles that play a direct role in anticancer immunotherapy. Of note, exosomes can transport their contents to specific cells, thereby exerting an impact on the phenotype and immune-regulatory functions of targeted cells. Therapeutic cancer vaccines, an emerging therapeutics of immunotherapy, could enhance antitumor immune responses by delivering a large number of tumor antigens, thereby augmenting the immune response against tumor cells. Therefore, the therapeutic rationale of cancer vaccines and exosome-based immunotherapy are almost similar to some extent, but some challenges have hindered their application in the clinical setting. Here, in this review, we first summarized the biogenesis, structure, compositions, and biological functions of exosomes. Then we described the roles of exosomes in cancer biology, particularly in tumor immunity. We also comprehensively reviewed current exosome-based anticancer vaccine development and we divided them into three types. Finally, we give some insights into clinical translation and clinical trial progress of exosome-based anticancer vaccines for future direction.

Keywords:  Exosomes; cancer vaccines; clinical translation; immunotherapy; tumor immunity

DOI:  https://doi.org/10.1016/j.canlet.2024.216989
Biochem Genet. 2024 Jun 05.

Exosome-Mediated Communication in Thyroid Cancer: Implications for Prognosis and Therapeutic Targets.

Yiwei Wang, Qiang Li, Xinrui Yang, Hanyu Guo, Tian Ren, Tianchi Zhang, Pantea Ghadakpour, Fu Ren.

  Thyroid cancer (THCA) is one of the most common malignancies of the endocrine system. Exosomes have significant value in performing molecular treatments, evaluating the diagnosis and determining tumor prognosis. Thus, the identification of exosome-related genes could be valuable for the diagnosis and potential treatment of THCA. In this study, we examined a set of exosome-related differentially expressed genes (DEGs) (BIRC5, POSTN, TGFBR1, DUSP1, BID, and FGFR2) by taking the intersection between the DEGs of the TCGA-THCA and GeneCards datasets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the exosome-related DEGs indicated that these genes were involved in certain biological functions and pathways. Protein‒protein interaction (PPI), mRNA‒miRNA, and mRNA-TF interaction networks were constructed using the 6 exosome-related DEGs as hub genes. Furthermore, we analyzed the correlation between the 6 exosome-related DEGs and immune infiltration. The Genomics of Drug Sensitivity in Cancer (GDSC), the Cancer Cell Line Encyclopedia (CCLE), and the CellMiner database were used to elucidate the relationship between the exosome-related DEGs and drug sensitivity. In addition, we verified that both POSTN and BID were upregulated in papillary thyroid cancer (PTC) patients and that their expression was correlated with cancer progression. The POSTN and BID protein expression levels were further examined in THCA cell lines. These findings provide insights into exosome-related clinical trials and drug development.

Keywords:  BID; Exosome; POSTN; Papillary thyroid cancer; Thyroid cancer

DOI:  https://doi.org/10.1007/s10528-024-10833-2
Mol Cancer. 2024 Jun 08. 23(1): 125

Exosomal circSIPA1L3-mediated intercellular communication contributes to glucose metabolic reprogramming and progression of triple negative breast cancer.

Yiran Liang, Fangzhou Ye, Dan Luo, Li Long, Yajie Wang, Yuhan Jin, Lei Wang, Yaming Li, Dianwen Han, Bing Chen, Wenjing Zhao, Lijuan Wang, Qifeng Yang.

   BACKGROUND: Breast cancer is the most common malignant tumor, and metastasis remains the major cause of poor prognosis. Glucose metabolic reprogramming is one of the prominent hallmarks in cancer, providing nutrients and energy to support dramatically elevated tumor growth and metastasis. Nevertheless, the potential mechanistic links between glycolysis and breast cancer progression have not been thoroughly elucidated.
METHODS: RNA-seq analysis was used to identify glucose metabolism-related circRNAs. The expression of circSIPA1L3 in breast cancer tissues and serum was examined by qRT-PCR, and further assessed its diagnostic value. We also evaluated the prognostic potential of circSIPA1L3 by analyzing a cohort of 238 breast cancer patients. Gain- and loss-of-function experiments, transcriptomic analysis, and molecular biology experiments were conducted to explore the biological function and regulatory mechanism of circSIPA1L3.
RESULTS: Using RNA-seq analysis, circSIPA1L3 was identified as the critical mediator responsible for metabolic adaption upon energy stress. Gain- and loss-of-function experiments revealed that circSIPA1L3 exerted a stimulative effect on breast cancer progression and glycolysis, which could also be transported by exosomes and facilitated malignant behaviors among breast cancer cells. Significantly, the elevated lactate secretion caused by circSIPA1L3-mediated glycolysis enhancement promoted the recruitment of tumor associated macrophage and their tumor-promoting roles. Mechanistically, EIF4A3 induced the cyclization and cytoplasmic export of circSIPA1L3, which inhibited ubiquitin-mediated IGF2BP3 degradation through enhancing the UPS7-IGF2BP3 interaction. Furthermore, circSIPA1L3 increased mRNA stability of the lactate export carrier SLC16A1 and the glucose intake enhancer RAB11A through either strengthening their interaction with IGF2BP3 or sponging miR-665, leading to enhanced glycolytic metabolism. Clinically, elevated circSIPA1L3 expression indicated unfavorable prognosis base on the cohort of 238 breast cancer patients. Moreover, circSIPA1L3 was highly expressed in the serum of breast cancer patients and exhibited high diagnostic value for breast cancer patients.
CONCLUSIONS: Our study highlights the oncogenic role of circSIPA1L3 through mediating glucose metabolism, which might serve as a promising diagnostic and prognostic biomarker and potential therapeutic target for breast cancer.

Keywords:  Breast cancer; Exosome; Glycolysis; IGF2BP3; Stemness; circSIPA1L3

DOI:  https://doi.org/10.1186/s12943-024-02037-4