bims-exocan 2023-06-25 papers

bims-exocan

Biomed News

on Exosomes roles in cancer

Issue of 2023–06–25
seven papers selected by
Muhammad Rizwan, COMSATS University

Exosomal miRNAs and breast cancer: A complex theranostics interlink with clinical significance.
Hypoxia derived exosomes promote the proliferation and metastasis of colorectal cancer through the regulation of HIF-1α/miR-4299/ZBTB4.
The biological function of tumor-derived extracellular vesicles on metabolism.
Large-scale Isolation of Exosomes Derived from NK Cells for Anti-tumor Therapy.
Surface-Engineered Extracellular Vesicles in Cancer Immunotherapy.
Exosomal miRNA-223-3p derived from tumor associated macrophages promotes pulmonary metastasis of breast cancer 4T1 cells.
Role of microRNA carried by small extracellular vesicles in urological tumors.

Biomarkers. 2023 Jun 23. 1-30

Exosomal miRNAs and breast cancer: A complex theranostics interlink with clinical significance.

Sayantanee Mukherjee, Rajib Dhar, Swathi Jonnalagadda, Sukhamoy Gorai, Sagnik Nag, Rishav Kar, Nobendu Mukerjee, Dattatreya Mukherjee, Rishabh Vatsa, Devi Arikketh, Anand Krishnan, Rohit Gundamaraju, Saurabh Kumar Jha, Athanasios Alexiou, Marios Papadakis.

  Breast cancer (BC) remains the most challenging global health crisis of the current decade, impacting a large population of females annually. In the field of cancer research, the discovery of extracellular vesicles (EVs), specifically exosomes (a subpopulation of EVs), has marked a significant milestone. In general, exosomes are released from all active cells but tumor cell-derived exosomes (TDXs) have a great impact (TDXs miRNAs, proteins, lipid molecules) on cancer development and progression. TDXs regulate multiple events in breast cancer such as tumor microenvironment remodeling, immune cell suppression, angiogenesis, metastasis (EMT-epithelial mesenchymal transition, organ-specific metastasis), and therapeutic resistance. In BC, early detection is the most challenging event, exosome-based BC screening solved the problem. Exosome-based BC treatment is a sign of the transforming era of liquid biopsy. It is also a promising therapeutic tool for breast cancer. Exosome research goes to closer precision oncology via a single exosome profiling approach. Our hope is that this review will serve as motivation for researchers to explore the field of exosomes and develop an efficient, and affordable theranostics approach for breast cancer.

Keywords:  Breast cancer; biomarker; exosome; metastasis; therapeutic

DOI:  https://doi.org/10.1080/1354750X.2023.2229537
Life Sci. 2023 Jun 21. pii: S0024-3205(23)00507-6. [Epub ahead of print] 121872

Hypoxia derived exosomes promote the proliferation and metastasis of colorectal cancer through the regulation of HIF-1α/miR-4299/ZBTB4.

Lunpo Wu, Meng Xue, Sanchuan Lai, Jingyu Chen, Yifeng Lin, Ning Ding, Jing Zhong, Shujie Chen, Liangjing Wang.

   AIMS: The biological functions of colorectal cancer (CRC) cell derived exosomes responding to hypoxic microenvironment and its underlying mechanisms remain unclear.
MAIN METHODS: Extracted exosomes were confirmed. CRC cells were incubated with hypoxic and normoxic exosomes and its biological behavior were analyzed. miRNA microarray were conducted. Cells were incubated with miRNAs mimics, inhibitors, or small interfering RNAs; expression of reporter constructs was measured in luciferase assays. Cells were transfected with Lentivirus vectors containing eGFP-miR-4299 overexpression (or ZBTB4 siRNA expression plasmid) and they were injected into BALB/C nude mice subcutaneously or by tail vein and the growth of xenograft tumors or lung metastasis were measured. The clinical significance of ZBTB4 was measured in tumor tissues and adjacent non-tumor tissues.
KEY FINDINGS: Hypoxic exosomes could tranfer to the recipient normoxic cells and promote the cell proliferation and migration. We found several miRNAs were significantly up-regulated in hypoxic exosomes and the expression levels of miR-4299 increased in both hypoxic cells and hypoxic exosomes. We observed that miR-4299 was upregulated in a HIF-1α dependent way. In addition, ectopic expression of miR-4299 promoted the tumor growth and metastasis in vitro and in vivo. ZBTB4, an identified direct target of miR-4299, could abrogate the effect on tumor growth and distant metastasis. The expression of ZBTB4 were decreased in tumor tissues compared with non-tumor colon tissues from patients.
SIGNIFICANCE: We demonstrated that in response to hypoxia, CRC cells had an increased production of exosomes. The hypoxia derived exosomes promote the proliferation and metastasis of colorectal cancer by exporting miR-4299 and modulating its target gene ZBTB4.

Keywords:  Colorectal cancer; Exosomes; Hypoxia; Metastasis; miRNAs

DOI:  https://doi.org/10.1016/j.lfs.2023.121872
Cell Commun Signal. 2023 Jun 22. 21(1): 150

The biological function of tumor-derived extracellular vesicles on metabolism.

Xiaoyu Fu, Junlong Song, Wei Yan, Bradley M Downs, Weixing Wang, Juanjuan Li.

  Multiple studies have shown that extracellular vesicles (EVs) play a key role in the process of information transfer and material transport between cells. EVs are classified into different types according to their sizes, which includes the class of exosomes. In comparison to normal EVs, tumor-derived EVs (TDEs) have both altered components and quantities of contents. TDEs have been shown to help facilitate an environment conducive to the occurrence and development of tumor by regulation of glucose, lipids and amino acids. Furthermore, TDEs can also affect the host metabolism and immune system. EVs have been shown to have multiple clinically useful properties, including the use of TDEs as biomarkers for the early diagnosis of diseases and using the transport properties of exosomes for drug delivery. Targeting the key bioactive cargoes of exosomes could be applied to provide new strategies for the treatment of tumors. In this review, we summarize the finding of studies focused on measuring the effects of TDE on tumor-related microenvironment and systemic metabolism. Video Abstract.

Keywords:  Extracellular vesicles (EVs); Glycolysis; Lipid metabolism; Metabolism; Tumor-derived exosomes (TDEs)

DOI:  https://doi.org/10.1186/s12964-023-01111-6
Bio Protoc. 2023 Jun 05. 13(11): e4693

Large-scale Isolation of Exosomes Derived from NK Cells for Anti-tumor Therapy.

Heyong Luo, Jing Zhang, Anqing Yang, Weiwei Ouyang, Shiqi Long, Xiaojin Lin, Na Yang, Zhiru Yang, Yingchun Zhang, Wei Yang, Qiyuan Che, Yuxin Yang, Ting Guo, Xing Zhao.

  Exosomes are lipid bilayer-enclosed vesicles, actively secreted by cells, containing proteins, lipids, nucleic acids, and other substances with multiple biological functions after entering target cells. Exosomes derived from NK cells have been shown to have certain anti-tumor effects and potential applications as chemotherapy drug carriers. These developments have resulted in high demand for exosomes. Although there has been large-scale industrial preparation of exosomes, they are only for generally engineered cells such as HEK 293T. The large-scale preparation of specific cellular exosomes is still a major problem in laboratory studies. Therefore, in this study, we used tangential flow filtration (TFF) to concentrate the culture supernatants isolated from NK cells and isolated NK cell-derived exosomes (NK-Exo) by ultracentrifugation. Through a series of characterization and functional verification of NK-Exo, the characterization, phenotype, and anti-tumor activity of NK-Exo were verified. Our study provides a considerably time- and labor-saving protocol for the isolation of NK-Exo.

Keywords:  Exosome; Immunotherapy; Natural killer cells; Tangential flow filtration; Ultracentrifugation

DOI:  https://doi.org/10.21769/BioProtoc.4693
Cancers (Basel). 2023 May 19. pii: 2838. [Epub ahead of print]15(10):

Surface-Engineered Extracellular Vesicles in Cancer Immunotherapy.

Vinith Johnson, Sunil Vasu, Uday S Kumar, Manoj Kumar.

  Extracellular vesicles (EVs) are lipid bilayer-enclosed bodies secreted by all cell types. EVs carry bioactive materials, such as proteins, lipids, metabolites, and nucleic acids, to communicate and elicit functional alterations and phenotypic changes in the counterpart stromal cells. In cancer, cells secrete EVs to shape a tumor-promoting niche. Tumor-secreted EVs mediate communications with immune cells that determine the fate of anti-tumor therapeutic effectiveness. Surface engineering of EVs has emerged as a promising tool for the modulation of tumor microenvironments for cancer immunotherapy. Modification of EVs' surface with various molecules, such as antibodies, peptides, and proteins, can enhance their targeting specificity, immunogenicity, biodistribution, and pharmacokinetics. The diverse approaches sought for engineering EV surfaces can be categorized as physical, chemical, and genetic engineering strategies. The choice of method depends on the specific application and desired outcome. Each has its advantages and disadvantages. This review lends a bird's-eye view of the recent progress in these approaches with respect to their rational implications in the immunomodulation of tumor microenvironments (TME) from pro-tumorigenic to anti-tumorigenic ones. The strategies for modulating TME using targeted EVs, their advantages, current limitations, and future directions are discussed.

Keywords:  apoptotic bodies; cancer immunotherapy; drug delivery system; exosomes; extracellular vesicles; immunomodulation; microvesicles; surface engineering; tumor immune microenvironment; tumor-secreted EVs

DOI:  https://doi.org/10.3390/cancers15102838
Transl Oncol. 2023 Jun 15. pii: S1936-5233(23)00101-8. [Epub ahead of print]35 101715

Exosomal miRNA-223-3p derived from tumor associated macrophages promotes pulmonary metastasis of breast cancer 4T1 cells.

Ziyuan Wang, Chen Zhang, Jian Guo, Wei Wang, Qin Si, Chong Chen, Yunping Luo, Zhaojun Duan.

  Research about the effect of exosomes derived from tumor associated macrophages (TAM-exos) in the distant organ metastasis of breast cancer is limited. In this study, we found that TAM-exos could promote the migration of 4T1 cells. Through comparing the expression of microRNAs in 4T1 cells, TAM-exos, and exosomes from bone marrow derived macrophages (BMDM-exos) by sequencing, miR-223-3p and miR-379-5p were screened out as two noteworthy differentially expressed microRNAs. Furthermore, miR-223-3p was confirmed to be the reason for the improved migration and metastasis of 4T1 cells. The expression of miR-223-3p was also increased in 4T1 cells isolated from the lung of tumor-bearing mice. Cbx5, which has been reported to be closely related with metastasis of breast cancer, was identified to be the target of miR-223-3p. Based on the information of breast cancer patients from online databases, miR-223-3p had a negative correlation with the overall survival rate of breast cancer patients within a three-year follow-up, while Cbx5 showed an opposite relationship. Taken together, miR-223-3p in TAM-exos can be delivered into 4T1 cells and exosomal miR-223-3p promotes pulmonary metastasis of 4T1 cells by targeting Cbx5.

Keywords:  Cbx5; Exosomes; Metastasis; TAMs; miR-223-3p

DOI:  https://doi.org/10.1016/j.tranon.2023.101715
Front Cell Dev Biol. 2023 ;11 1192937

Role of microRNA carried by small extracellular vesicles in urological tumors.

Yiping Mao, Mengting Zhang, Lanfeng Wang, Yukang Lu, Xinyi Hu, Zhiping Chen.

  Small extracellular vesicles (sEVs) are minute vesicles secreted by various cells that are capable of transporting cargo, including microRNAs, between donor and recipient cells. MicroRNAs (miRNAs), small non-coding RNAs approximately 22 nucleotides in length, have been implicated in a wide array of biological processes, including those involved in tumorigenesis. Emerging evidence highlights the pivotal role of miRNAs encapsulated in sEVs in both the diagnosis and treatment of urological tumors, with potential implications in epithelial-mesenchymal transition, proliferation, metastasis, angiogenesis, tumor microenvironment and drug resistance. This review provides a brief overview of the biogenesis and functional mechanisms of sEVs and miRNAs, followed by a summarization of recent empirical findings on miRNAs encapsulated in sEVs from three archetypal urologic malignancies: prostate cancer, clear cell renal cell carcinoma, and bladder cancer. We conclude by underscoring the potential of sEV-enclosed miRNAs as both biomarkers and therapeutic targets, with a particular focus on their detection and analysis in biological fluids such as urine, plasma, and serum.

Keywords:  MicroRNAs; barrett esophagus; diagnosis; small extracelllular vesicles; therapy; urological tumors

DOI:  https://doi.org/10.3389/fcell.2023.1192937