bims-exocan 2022-12-25 papers

bims-exocan

Biomed News

on Exosomes roles in cancer

Issue of 2022‒12‒25
ten papers selected by
Muhammad Rizwan
COMSATS University

Research progress of exosomes as drug carriers in cancer and inflammation.
Gastric Cancer Cell-Derived Exosomal GRP78 Enhances Angiogenesis upon Stimulation of Vascular Endothelial Cells.
Potential Role of Tumor-Derived Exosomes in Non-Small-Cell Lung Cancer in the Era of Immunotherapy.
Cancer-associated fibroblast-derived exosome miR-181b-3p promotes the occurrence and development of colorectal cancer by regulating SNX2 expression.
MiR-375 and miR-21 as Potential Biomarkers of Prostate Cancer: Comparison of Matching Samples of Plasma and Exosomes.
Significance of exosomes in hepatocellular carcinoma.
A comprehensive study based on exosome-related immunosuppression genes and tumor microenvironment in hepatocellular carcinoma.
Exploring breast cancer exosomes for novel biomarkers of potential diagnostic and prognostic importance.
Exosomal microRNAs Targeting TP53 Gene as Promising Prognostic Markers for Head and Neck Squamous Cell Carcinoma.
Profiling of Tumor Cell-delivered Exosome by Surface Enhanced Raman Spectroscopy-based Biosensor for Evaluation of Nasopharyngeal Cancer Radioresistance.

J Drug Target. 2022 Dec 21. 1-39

Research progress of exosomes as drug carriers in cancer and inflammation.

Qixiang Feng, Yu Zhang, Yuelin Fang, Xinru Kong, Zhijing He, Jianbo Ji, Xiaoye Yang, Guangxi Zhai.

  Extracellular vesicles (EVs) could be produced by most cells and play an important role in disease development. As a subtype of EVs, exosomes exhibit suitable size, rich surface markers and diverse contents, making them more appealing as potential drug carriers. Compared with traditional synthetic nanoparticles, exosomes possess superior biocompatibility and much lower immunogenicity. This work reviewed the most up-to-date research progress of exosomes as carriers for nucleic acids, proteins and small molecule drugs for cancer and inflammation management. The drug loading strategies and potential cellular uptake behavior of exosomes are highlighted, trying to provide reference for future exosome design and application.

Keywords:  cancer; drug delivery; exosomes; extracellular vesicles; inflammation

DOI:  https://doi.org/10.1080/1061186X.2022.2162059
Curr Issues Mol Biol. 2022 Dec 06. 44(12): 6145-6157

Gastric Cancer Cell-Derived Exosomal GRP78 Enhances Angiogenesis upon Stimulation of Vascular Endothelial Cells.

Kanako Iha, Akane Sato, Hsin-Yi Tsai, Hikaru Sonoda, Satoshi Watabe, Teruki Yoshimura, Ming-Wei Lin, Etsuro Ito.

  Exosomes containing glucose-regulated protein 78 (GRP78) are involved in cancer malignancy. GRP78 is thought to promote the tumor microenvironment, leading to angiogenesis. No direct evidence for this role has been reported, however, mainly because of difficulties in accurately measuring the GRP78 concentration in the exosomes. Recently, exosomal GRP78 concentrations were successfully measured using an ultrasensitive ELISA. In the present study, GRP78 concentrations in exosomes collected from gastric cancer AGS cells with overexpression of GRP78 (OE), knockdown of GRP78 (KD), or mock GRP78 (mock) were quantified. These three types of exosomes were then incubated with vascular endothelial cells to examine their effects on endothelial cell angiogenesis. Based on the results of a tube formation assay, GRP78-OE exosomes accelerated angiogenesis compared with GRP78-KD or GRP78-mock exosomes. To investigate the mechanisms underlying this effect, we examined the Ser473 phosphorylation state ratio of AKT, which is involved in the angiogenesis process, and found that AKT phosphorylation was increased by GRP78-OE exosome application to the endothelial cells. An MTT assay showed that GRP78-OE exosome treatment increased the proliferation rate of endothelial cells, and a wound healing assay showed that this treatment increased the migration capacity of the endothelial cells. These findings demonstrated that GRP78-containing exosomes promote the tumor microenvironment and induce angiogenesis.

Keywords:  GRP78; angiogenesis; exosome; gastric cancer cell; ultrasensitive ELISA; vascular endothelial cell

DOI:  https://doi.org/10.3390/cimb44120419
Life (Basel). 2022 Dec 14. pii: 2104. [Epub ahead of print]12(12):

Potential Role of Tumor-Derived Exosomes in Non-Small-Cell Lung Cancer in the Era of Immunotherapy.

Alfredo Tartarone, Rosa Lerose, Marina Tartarone, Michele Aieta.

  Lung cancer, of which non-small-cell lung cancer (NSCLC) represents about 80% of all cases, is the second most common cancer diagnosed in the general population and one of the major causes of cancer-related deaths worldwide. Overall, the outcomes of patients with advanced NSCLC are still disappointing despite advances in diagnosis and treatment. In recent years immune-checkpoint inhibitors (ICIs), administered alone or in combination with chemotherapy, have revolutionized the treatment landscape of patients with advanced non-small-cell lung cancer. However, until now, tissue expression of PD-L1 and tumor mutation burden represent the only available biomarkers for NSCLC patients treated with ICIs. A growing body of evidence showed that tumor-derived exosomes (TDEs) have the PD-L1 protein on their surface and that they are involved in angiogenesis, tumor growth, invasion, metastasis and immune escape. This review focused on the potential clinical applications of TDEs in NSCLC, including their possible role as a biomarker for prognosis and disease monitoring in patients undergoing immunotherapy.

Keywords:  exosomes; immune-checkpoint inhibitors; liquid biopsy; non-small-cell lung cancer; tumor-derived exosomes

DOI:  https://doi.org/10.3390/life12122104
Biochem Biophys Res Commun. 2022 Dec 10. pii: S0006-291X(22)01691-6. [Epub ahead of print]641 177-185

Cancer-associated fibroblast-derived exosome miR-181b-3p promotes the occurrence and development of colorectal cancer by regulating SNX2 expression.

Yimei Jiang, Qingqing Qiu, Xiaoqian Jing, Zijia Song, Yaqi Zhang, Changgang Wang, Kun Liu, Feng Ye, Xiaopin Ji, Fangxiu Luo, Ren Zhao.

  Tumor microenvironment (TME) (e.g., stromal cells) has been closely related to the pathological process of colorectal cancer (CRC). In TME, tumor-associated fibroblasts (CAFs) are the main stromal cells. The studies have showed that CAFs promoted tumor growth and metastasis in CRC and led to poor prognosis. Mounting evidence indicates that CAFs-mediated exosomes regulate the pathological process of neighboring tumor cells through the transmission of miRNAs. In our study, we aimed to explore the function of CAFs-derived exosome miR-181b-3p in CRC. First, the expression of miR-181b-3p in CRC was found to be up-regulated and its expression was dramatically up-regulated in CRC cells after co-incubation of CAFs-mediated exosomes with CRC cells. Then, it was found that the CAFs-derived exosomes were markedly enhanced the proliferation and migration of the CRC cells, and substantially reduced apoptosis. To elucidate the influence of CAFs-derived exosome miR-181b-3p on CRC, we overexpressed and knocked down the miR-181b-3p expression in CAFs, respectively. It was found that miR-181b-3p significantly increased the proliferation and migration of CRC cells. Furthermore, we conducted in vivo experiments. Finally, we demonstrated that CAF-derived exosome miR-181b-3p regulated sorting nexin 2 (SNX2) expression in CRC cells by bioinformatics prediction combined with luciferase reporter assay. Further cellular and animal experiments jointly elucidated that miR-181b-3p promoted the pathological process of CRC by SNX2 expression. In brief, our results demonstrated that CAFs-derived exosome miR-181b-3p promoted the pathogenesis of CRC by regulating SNX2 expression, which provides a novel idea for CRC treatment.

Keywords:  CAFs; CRC; Exosomes; SNX2; miR-181b-3p

DOI:  https://doi.org/10.1016/j.bbrc.2022.12.026
Genes (Basel). 2022 Dec 09. pii: 2320. [Epub ahead of print]13(12):

MiR-375 and miR-21 as Potential Biomarkers of Prostate Cancer: Comparison of Matching Samples of Plasma and Exosomes.

Suzana Matijašević Joković, Zorana Dobrijević, Nevena Kotarac, Lidija Filipović, Milica Popović, Aleksandra Korać, Ivan Vuković, Dušanka Savić-Pavićević, Goran Brajušković.

  MiR-21 and miR-375 have been reported as dysregulated in prostate cancer (PCa) in multiple previous studies. Still, variable or even opposing data for the expression of these microRNAs in PCa were found, and their potential biomarker properties remain elusive. In an attempt to clarify their significance as PCa biomarkers, as well as to compare different types of specimens as a source of relevant microRNAs, we used plasma and matching plasma-derived exosomes from patients with PCa and patients with benign prostatic hyperplasia (BPH). Plasma and exosomes were obtained from 34 patients with PCa and 34 patients with BPH, and their levels of expression of miR-21 and miR-375 were determined by RT-qPCR. We found no significant difference in the level of expression of these microRNAs in plasma and exosomes between patients with PCa and BPH. The level of exosomal miR-21 was elevated in PCa patients with high serum PSA values, as well as in patients with aggressive PCa, while for plasma samples, the results remained insignificant. For miR-375, we did not find an association with the values of standard prognostic parameters of PCa, nor with cancer aggressiveness. Therefore, our results support the potential prognostic role of exosomal miR-21 expression levels in PCa.

Keywords:  exosomes; miR-21; miR-375; microRNAs; plasma; prostate cancer

DOI:  https://doi.org/10.3390/genes13122320
Front Oncol. 2022 ;12 1056379

Significance of exosomes in hepatocellular carcinoma.

GuoYun Wang, GaiXiang Luo, MeiJing Zhao, HuiLai Miao.

  Among the most prevalent cancers in the world, hepatocellular carcinoma (HCC) has a high mortality rate. The diagnosis and management of HCC are presently hindered by difficulties in early detection and suboptimal treatment outcomes. Exosomes have been shown to play an important role in hepatocarcinogenesis and can also be used for diagnosis and treatment. In this review, we discussed the research progress on exosomes in hepatocarcinogenesis development, tumor microenvironment remodeling, treatment resistance, and immunosuppression. HCC can be diagnosed and treated by understanding the pathogenesis and identifying early diagnostic markers. This review will be a significant reference for scholars with an initial understanding of the field to fully understand the role of exosomes in the organism.

Keywords:  development; drug resistance; exosomes; hepatocellular carcinoma; microenvironment; treatments

DOI:  https://doi.org/10.3389/fonc.2022.1056379
BMC Cancer. 2022 Dec 22. 22(1): 1344

A comprehensive study based on exosome-related immunosuppression genes and tumor microenvironment in hepatocellular carcinoma.

Zhan Yang, Xinmiao Li, Chaoran Pan, Yifei Li, Lifan Lin, Yan Jin, Jianjian Zheng, Zhengping Yu.

  BACKGROUND: Exosomes play an important role in the tumor microenvironment (TME) and the mechanisms of tumor immune escape in hepatocellular carcinoma (HCC). It is known that immunosuppressive genes, involved in the processes of tumor immunosuppression, are associated with cancer progression. This study aimed to explore the prognostic values of exosome-related immunosuppression genes (ERIGs) in HCC.METHODS: The RNA-seq transcriptome data of 374 HCC patients were obtained from the Cancer Genome Atlas (TCGA) database. The TCGA cohort was randomly divided into the training cohort and validation cohort in a 1:1 ratio. WGCNA analysis and Pearson correlation analysis were used to identify ERIGs. The Lasso regression method was used to construct a 5-ERIG signature. The prognostic value of our signature was examined in the First Affiliated Hospital of Wenzhou Medical University (FAHWMU) cohort.
RESULTS: Univariate Cox regression analysis was used to screen prognostic ERIGs. Subsequently, these prognostic ERIGs were included in Lasso regression analyses to identify 5 key ERIGs (ASAP1, IARS1, GTF3C2, TPD5L2 and SLC52A2) and construct a 5-ERIG signature. The patients in the low-risk group had better prognosis than those in the high-risk group. Univariate and multivariate cox regression revealed that risk score was an independent prognostic risk factor of HCC. Gene set enrichment analysis (GSEA) showed that this signature was highly associated with TME-related pathways. Subsequent analyses revealed the potential role of the signature in regulating the TME in HCC. In addition, a lower immunotherapy score was found in patients with high risk-score. Of note, this signature was confirmed to have a good performance in predicting HCC prognosis in the FAHWMU cohort. Moreover, knockdown of 5 ERIGs of this signature contributed to the suppression the Hep3B cell proliferation.
CONCLUSIONS: We generated a novel prognostic 5-ERIG signature to accurately predict the prognosis of patients with HCC, and this signature may serve as an indicator of immunotherapy for HCC.

Keywords:  Exosome; Hepatocellular carcinoma; Immunosuppressive gene; Immunotherapy; Tumor microenvironment

DOI:  https://doi.org/10.1186/s12885-022-10463-0
3 Biotech. 2023 Jan;13(1): 7

Exploring breast cancer exosomes for novel biomarkers of potential diagnostic and prognostic importance.

Dhananjay B Alagundagi, Sudeep D Ghate, Vinay Kumar J Rajendra, Pavan Gollapalli, Vijith V Shetty, Caren D'Souza, Praveenkumar Shetty, Prakash Patil.

  The comprehensive bioinformatics analysis of breast cancer exosomes revealed that HSP90AA1, CCT2, and ENO1 were novel hub genes in the giant protein-protein interaction network of 110 exosomal proteins. Exosomes and their cargo such as discrete proteins, nucleic acids, and lipids are having potential role in the pathophysiology of breast cancer (BC). This study showed that the identified hub genes were particularly abundant in GO and KEGG pathways relevant to the positive regulation of telomerase. In addition, these hub genes were found to be considerably overexpressed in breast adenocarcinoma patients compared to healthy controls, and further, this overexpression is linked to the poor prognosis in BC patients. Furthermore, the ROC analysis revealed that CCT2 gene has strong diagnostic and prognostic value for BC. Additionally, this in silico analysis found that the anticancer agents and HSP90 inhibitors such as ganetespib, retaspimycin, and tanespimycin would have considerable potential in the treatment of BC. Overall, this study findings imply that HSP90AA1, a molecular chaperon and CCT2, a chaperonin would serve as diagnostic and prognostic biomarkers, respectively, for BC. However, these findings need to be further confirmed by laboratory and clinical studies for validating their potential applications.Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03422-w.

Keywords:  Chaperone; Chaperonin; Exosomes; Hub genes; Network biology; Protein–protein interaction

DOI:  https://doi.org/10.1007/s13205-022-03422-w
Glob Med Genet. 2022 Dec;9(4): 277-286

Exosomal microRNAs Targeting TP53 Gene as Promising Prognostic Markers for Head and Neck Squamous Cell Carcinoma.

Vijayashree Priyadharsini Jayaseelan, Paramasivam Arumugam.

  Statement of Problem MicroRNAs are small non-coding RNAs that regulate an array of functions by targeting crucial genes. A significant dysregulation in the TP53 profile has been observed in the head and neck squamous cell carcinoma (HNSCC) patients. Hence, the present in silico study was designed to identify those microRNAs which target TP53 gene and demonstrate their differential expression in HNSCC cases. Materials and Methods The study was extended further to explore their exosomal location using database such as EVmiRNA and ExoCarta. The study follows an observational in silico design. Computational tool miRDB was used identify the microRNA targets of TP53 gene. The UALCAN server was used to ascertain the expression of microRNA in HNSCC cases derived from the Cancer Gene Atlas dataset. The survival of HNSCC patients based on the differential expression microRNA markers were recorded. Further, each of the microRNA was queried for their exosomal presence using EVmiRNA. Results About 102 microRNA targets of TP53 gene with a target score in the range of 95-50 were identified. The differential expression data for 52 microRNAs was retrieved from the UALCAN database. The microRNAs hsa-miR-421, hsa-miR-548f-5p, and hsa-let-7c-5p were found to be differentially expressed with marked influence over the survival of HNSCC patients. Furthermore, hsa-miR-421 and hsa-let-7c-5p were found to have an exosomal origin especially in body fluids such as blood and saliva. Conclusion The results accumulated from the present study identified three microRNAs which can affect the functions of TP53 gene and bring about serious outcomes in HNSCC patients. The microRNAs of exosomal origin targeting TP53 gene in HNSCC patients can be a promising prognostic marker, which can be further used as a therapeutic lead by designing inhibitors.

Keywords:  HNSCC; TP53; exosomes; microRNAs; theragnostic

DOI:  https://doi.org/10.1055/s-0042-1758204
Adv Healthc Mater. 2022 Dec 17. e2202482

Profiling of Tumor Cell-delivered Exosome by Surface Enhanced Raman Spectroscopy-based Biosensor for Evaluation of Nasopharyngeal Cancer Radioresistance.

Qiong Wu, Qin Ding, Wanzun Lin, Youliang Weng, Shangyuan Feng, Rong Chen, Chuanben Chen, Sufang Qiu, Duo Lin.

  Although the advancement of radiotherapy significantly improved the survival of nasopharyngeal cancer (NPC), radioresistance associated with recurrence and poor outcomes still remains a daunting challenge in the clinical scenario. Currently, effective biomarkers and convenient detection methods for predicting radioresistance have not been well established. Here, the surface-enhanced Raman spectroscopy (SERS) combined with proteomics was employed to firstly profile the characteristic spectral patterns of exosomes secreted from self-established NPC radioresistance cells, and revealed specific variations of proteins expression during radioresistance formation, including collagen alpha-2 (I) chain (COL1A2) that is associated with a favorable prognosis in NPC and is negatively associated with DNA repair scores and DNA repair-related genes via bioinformatic analysis. Furthermore, deep learning model-based diagnostic model was generated to accurately identify the exosomes from radioresistance group. Our work demonstrates the promising potential of exosomes as a novel biomarker for predicting the radioresistance and develops a rapid and sensitive liquid biopsy method that would provide a personalized and precise strategy for clinical NPC treatment. This article is protected by copyright. All rights reserved.

Keywords:  Nasopharyngeal cancer; biomarker; exosome; radiotherapy; surface-enhanced Raman spectroscopy

DOI:  https://doi.org/10.1002/adhm.202202482