bims-exocan 2023-03-05 papers

bims-exocan

Biomed News

on Exosomes roles in cancer

Issue of 2023–03–05
ten papers selected by
Muhammad Rizwan, COMSATS University

Presence and prospects of exosomal circRNAs in cancer (Review).
Exosome Mediated Cancer Therapeutic Approach:Present Status and Future Prospectives.
Transfer of exosomal microRNAs confers doxorubicin resistance in osteosarcoma cells.
The Diagnostic and Therapeutic Prospects of Exosomes in Ovarian Cancer.
Tumour‑derived exosomes and their emerging roles in leukaemia (Review).
Exosomes as natural nanocarrier-based drug delivery system: recent insights and future perspectives.
Serum exosomes from epithelial ovarian cancer patients contain LRP1, which promotes the migration of epithelial ovarian cancer cell.
Recent advances in extracellular vesicles in gastrointestinal cancer and lymphoma.
Influence of Exosomes on Astrocytes in the Pre-Metastatic Niche of Lung Cancer Brain Metastases.
Exosome-Encapsulated miR-31, miR-192, and miR-375 Serve as Clinical Biomarkers of Gastric Cancer.

Int J Oncol. 2023 Apr;pii: 47. [Epub ahead of print]62(4):

Presence and prospects of exosomal circRNAs in cancer (Review).

Junjie Cui, Jiaqi Wang, Lianyu Liu, Changwen Zou, Ying Zhao, Zhenyu Xue, Xiaoxiong Sun, Tao Jiang, Jun Song.

  Exosomes are nanoscale extracellular vesicles secreted by parent cells and they are present in most bodily fluids, are able to carry active substances through intercellular transport and mediate communication between different cells, in particular those active in cancer. Circular RNAs (circRNAs) are novel noncoding RNAs expressed in most eukaryotic cells and are involved in various physiological and pathological processes, particularly in the occurrence and progression of cancer. Numerous studies have indicated a close relationship between circRNAs and exosomes. Exosomal circRNAs (exo‑circRNAs) are a type of circRNA enriched in exosomes that may participate in the progression of cancer. Based on this, exo‑circRNAs may have an important role in malignant behavioral manifestations of cancer and hold great promise in the diagnosis and treatment of cancer. The present review gives an introduction to the origin and functions of exosomes and circRNAs and elaborates on the mechanisms of exo‑circRNAs in cancer progression. The biological functions of exo‑circRNAs in tumorigenesis, development and drug resistance, as well as their role as predictive biomarkers, were discussed.

Keywords:  cancer; circRNA; exosome; exo‑circRNAs

DOI:  https://doi.org/10.3892/ijo.2023.5495
Asian Pac J Cancer Prev. 2023 Feb 01. pii: 90481. [Epub ahead of print]24(2): 363-373

Exosome Mediated Cancer Therapeutic Approach:Present Status and Future Prospectives.

Anitha Roy, Smiline Girija As, Pitchaipillai Sankar Ganesh, Muthupandian Saravanan, Basil Sunny.

  The unique extracellular vesicles (EVs) or exosomes formed by the sequential invagination of the plasma membrane are diverse and encompass important constituents with biological functions. Speculations on its cell independent biological functions are significant and pose them as vital biomarkers and as drug delivery vehicles especially in cancer. EVs possess theragnostic values and are known to elicit specific immune response. Exosomes can also serve as potential nanocarriers for delivering miRNA, siRNA, anti-cancer drugs and membrane-associated proteins. Exosomes play a crucial role in regulating tumour progression, metastasis, and angiogenesis. This review thus portrays the multiple facets of exosomes, in concert with the source for exosomes production and further on its regulation and intercellular communication. The review also explores the recent advances, present status and the future prospective in the application of exosomes in cancer therapeutics and cancer diagnostics.

Keywords:  cancer-therapeutics; drug delivery vehicles; exosomes; immuno-therapy

DOI:  https://doi.org/10.31557/APJCP.2023.24.2.363
Mol Med Rep. 2023 Apr;pii: 86. [Epub ahead of print]27(4):

Transfer of exosomal microRNAs confers doxorubicin resistance in osteosarcoma cells.

Tao Cai, Chunlin Zhang, Taichen Zhan.

  Osteosarcoma (OS) is the commonest primary malignant bone tumor in children and adolescents. However, chemotherapy resistance is a major challenge for the treatment of OS. Exosomes have been reported to serve an increasingly important role in different stages of tumor progression and chemotherapy resistance. The present study investigated whether exosomes derived from doxorubicin‑resistant OS cells (MG63/DXR) could be taken up in doxorubicin‑sensitive OS cells (MG63) and induce a doxorubicin‑resistant phenotype. MDR‑1, as the specific mRNA of chemoresistance, can be transferred by exosomes from MG63/DXR cells to MG63 cells. In addition, the present study identified 2,864 differentially expressed miRNAs (456 upregulated and 98 downregulated with fold‑change >2.0, P<5x10‑2, and FDR<0.05) in all three sets of exosomes from MG63/DXR cells and MG63 cells. The related miRNAs and pathways of exosomes involved in the doxorubicin resistance were identified by bioinformatic analysis. A total of 10 randomly selected exosomal miRNAs were dysregulated in exosomes from MG63/DXR cells relative to MG63 cells by reverse transcription‑quantitative PCR detection. As a result, miR‑143‑3p was found high expressed in exosomes from doxorubicin‑resistant OS cells compared with doxorubicin‑sensitive OS cells and upregulation of exosomal miR‑143‑3p abundance associated with the poor chemotherapeutic response to OS cells. Briefly, transfer of exosomal miR‑143‑3p confers doxorubicin resistance in osteosarcoma cells.

Keywords:  chemoresistance; exosome; microRNA; osteosarcoma

DOI:  https://doi.org/10.3892/mmr.2023.12973
BJOG. 2023 Feb 28.

The Diagnostic and Therapeutic Prospects of Exosomes in Ovarian Cancer.

Qianrun Chen, Jiayan Shi, Danhua Ruan, Ce Bian.

  Exosomes are nano-sized vesicles derived from the endosomal system and involved in many biological and pathological processes. Emerging evidence has demonstrated that exosomes with cell-specific constituents are associated with the tumorigenesis and progression of ovarian cancer. Therefore, exosomes derived from ovarian cancers can be potential diagnostic biomarkers and therapeutic targets. In this review, we briefly present the biological characteristics of exosomes and the recent advances in isolating and detecting exosomes. Furthermore, we summarize the many functions of exosomes in ovarian cancer, hoping to provide a theoretical basis for clinical applications of exosomes in the diagnosis and treatment of ovarian cancer.

Keywords:  Biomarker; Exosomes; Ovarian cancer; Therapy

DOI:  https://doi.org/10.1111/1471-0528.17446
Exp Ther Med. 2023 Mar;25(3): 126

Tumour‑derived exosomes and their emerging roles in leukaemia (Review).

Lei Chen, Ting Xie, Bing Wei, Da-Lin Di.

  Exosomes are small vesicles with a diameter of ~40-100 nm that are secreted by the majority of endogenous cells under normal and pathological conditions. They contain abundant proteins, lipids, microRNAs, and biomolecules such as signal transduction molecules, adhesion factors and cytoskeletal proteins, and play an important role in exchanging materials and transmitting information between cells. Recent studies have shown that exosomes are involved in the pathophysiology of leukaemia by affecting the bone marrow microenvironment, apoptosis, tumour angiogenesis, immune escape and chemotherapy resistance. Furthermore, exosomes are potential biomarkers and drug carriers for leukaemia, impacting the diagnosis and treatment of leukaemia. The present study describes the biogenesis and general characteristics of exosomes, and then highlight the emerging roles of exosomes in different types of leukaemia. Finally, the value of clinical application of exosomes as biomarkers and drug carriers is discussed with the aim to provide novel strategies for the treatment of leukaemia.

Keywords:  biomarkers; drug carriers; exosomes; leukaemia; vaccine development

DOI:  https://doi.org/10.3892/etm.2023.11825
3 Biotech. 2023 Mar;13(3): 101

Exosomes as natural nanocarrier-based drug delivery system: recent insights and future perspectives.

Srijita Sen, Joyal Xavier, Nitesh Kumar, Mohammad Zaki Ahmad, Om Prakash Ranjan.

  Exosomes are nanosized (size ~ 30-150 nm) natural vesicular structures released from cells by physiological processes or pathological circumstances. Exosomes are growing in popularity as a result of their many benefits over conventional nanovehicles, including their ability to escape homing in the liver or metabolic destruction and their lack of undesired accumulation before reaching their intended targets. Various therapeutic molecules, including nucleic acids, have been incorporated into exosomes by different techniques, many of which have shown satisfactory performance in various diseases. Surface-modified exosomes are a potentially effective strategy, and it increases the circulation time and produces the specific drug target vehicle. In this comprehensive review, we describe composition exosomes biogenesis and the role of exosomes in intercellular signaling and cell-cell communications, immune responses, cellular homeostasis, autophagy, and infectious diseases. In addition, we discuss the role of exosomes as diagnostic markers, and their therapeutic and clinical implications. Furthermore, we addressed the challenges and outstanding developments in exosome research and discuss future perspectives. In addition to the current status of exosomes as a therapeutic carrier, the lacuna in the clinical development lifecycles along with the possible strategies to fill the lacuna have been addressed.

Keywords:  Biogenesis; Clinical trial; Drug loading; Exosomes; Extracellular vesicles; Proteins; RNA; Surface modification

DOI:  https://doi.org/10.1007/s13205-023-03521-2
Mol Cell Proteomics. 2023 Feb 24. pii: S1535-9476(23)00030-0. [Epub ahead of print] 100520

Serum exosomes from epithelial ovarian cancer patients contain LRP1, which promotes the migration of epithelial ovarian cancer cell.

Wei Zhou, Jiachen Ma, Han Zhao, Qing Wang, Xiaoli Guo, Linna Chen, Zhonghui Cao, Jiahao Xu, Bei Zhang, Xueyan Zhou.

  Ovarian cancer is a gynecological tumor with extremely high mortality and poor prognosis. Exosomes derived from tumor cells contain abundant proteins that may influence tumor metastasis. The purpose of our study was to explore the proteomic profile of serum exosomes from Epithelial ovarian cancer (EOC) patients and to find potential diagnostic markers for EOC. We obtained purified exosomes from serum using ultracentrifugation. Migration assay was used to evaluate the effects of exosomes on the migration of EOC cells. Proteomic profile of serum exosomes was analyzed by Liquid chromatogram-tande mass spectrometry (LC-MS/MS). The level of LRP1 in serum and serum exosomes were determined by Enzyme-Linked Immunosorbent Assay (ELISA). Western blot and Immunohistochemistry were used to determine the level of LRP1 in tissues. Moreover, we performed small-interfering RNA-mediated knockdown of LRP1 in EOC cells to obtain SI-LRP1-Exos and SI-NC-Exos. The detailed mechanisms by which exosomal LRP1 affected the migration of EOC cells in vitro and in vivo were also explored. We found that serum exosomes from EOC patients contributed to the migration of EOC cells. The level of serum exosomal LRP1 of EOC patients was significantly upregulated compared with that of healthy volunteers, which was consistent with the result of ELISA. We found that exosomal LRP1 regulated the expression of MMP2 and MMP9 through ERK signaling pathway and affected the migration of EOC cells in vitro and in vivo. Therefore, we propose that exosomal LRP1 contributes to the migration of EOC and may act as an important diagnostic and prognostic biomarker of EOC.

Keywords:  Epithelial ovarian cancer; Exosome; Low-density lipoprotein receptor-related protein 1; Migration; Proteomics

DOI:  https://doi.org/10.1016/j.mcpro.2023.100520
Cancer Sci. 2023 Feb 27.

Recent advances in extracellular vesicles in gastrointestinal cancer and lymphoma.

Motoyuki Otsuka, Ai Kotani.

  Extracellular vesicles (EVs) are intercellular communication agents that transfer microRNAs (miRNAs), other non-coding RNAs (ncRNAs), messenger RNAs (mRNAs), proteins, lipids, metabolites, and other molecules from donor cells (e.g., cancer cells) to recipient cells (e.g., stromal cells). In 2007, miRNAs were reported to be abundant among the ncRNAs present in EVs. Since then, many studies have investigated the functions of miRNAs and have attempted to apply these molecules to aid in the diagnosis and treatment of cancer. Research on EVs has expanded, particularly in the field of cancer, because cancer cells heavily secrete EVs. The cargo of these EVs, especially those in small EVs such as exosomes, is assumed to work cooperatively and significantly in the tumor microenvironment and to promote metastasis. In this review, we first summarize recent studies on EVs in gastrointestinal cancer and highlight studies on human satellite II RNAs, which are a type of ncRNA found in EVs and possessing repetitive sequences. Second, since several recent studies have revealed that phospholipids, which are components of EV membranes, play important roles in intercellular communication and in the generation of lipid mediators in the tumor microenvironment, we review the reported roles of these molecules and discuss their potential use in the design of new cancer treatments.

Keywords:  Epstein-Barr virus; Extracellular vesicle; gastrointestinal cancer; lymphoma; phospholipids

DOI:  https://doi.org/10.1111/cas.15771
Biol Proced Online. 2023 Mar 01. 25(1): 5

Influence of Exosomes on Astrocytes in the Pre-Metastatic Niche of Lung Cancer Brain Metastases.

Lingyun Ye, Yinfei Wu, Juan Zhou, Mengqing Xie, Zhemin Zhang, Chunxia Su.

   BACKGROUND: Lung cancer is the most common cause of cancer-related death globally. There are several reasons for this high mortality rate, including metastasis to multiple organs, especially the brain. Exosomes play a pivotal role in tumor metastasis by remodeling the microenvironment of remote target organs and promoting the pre-metastatic niche's formation. Since astrocytes are indispensable for maintaining the homeostasis of brain microenvironment, it's of great interest to explore the influence of lung cancer cell-derived exosomes on astrocytes to further understand the mechanism of lung cancer brain metastasis.
RESULTS: Twenty four h after co-culture of H1299 cell-derived exosomes and SVG P12 cells, the viability of astrocytes decreased and the apoptosis increased. The levels of cytokines in the supernatant including GROα/CXCL1, IFN-γ, IL-3, IL-5, IL-15, LIF, M-CSF, NGF, PDGF, and VEGF were significantly enhanced, while IL-7 secretion was significantly reduced. Meanwhile, apoptosis-related proteins MAP2K1, TUBA1C, RELA, and CASP6 were up-regulated. And the differentially expressed proteins were involved in regulating metabolic pathways.
CONCLUSION: Exosomes of H1299 could induce apoptosis of astrocytes as well as promote their secretion of cytokines that were conducive to the formation of the inflammatory microenvironment and immunosuppressive microenvironment, and affect their metabolic pathways, thus facilitating the formation of pre-metastatic niche in lung cancer brain metastases.

Keywords:  Astrocyte; Exosome; Lung cancer brain metastases; Pre-metastatic niche

DOI:  https://doi.org/10.1186/s12575-023-00192-4
J Oncol. 2023 ;2023 7335456

Exosome-Encapsulated miR-31, miR-192, and miR-375 Serve as Clinical Biomarkers of Gastric Cancer.

Jing He, Jing Wu, Shiyang Dong, Jing Xu, Jian Wang, Xin Zhou, Zhuqing Rao, Wen Gao.

In recent years, microRNAs (miRNAs) derived from exosomes have been attracting attention as novel clinical biomarkers in a variety of cancers. In this study, plasma samples from 60 gastric cancer (GC) patients and 63 healthy individuals were collected, and the exosomal microRNAs (ex-miRNAs) were isolated. We determined the specific ex-miRNAs through miRNA microarray and a database of differentially expressed miRNAs called dbDEMC. Then, the expression levels of exosomal miR-31, miR-192, and miR-375 were analyzed by quantitative polymerase chain reaction (qRT-PCR). Compared to the matched controls, exosomal miR-31, miR-375, and miR-192 were significantly upregulated in GC patients. Also, they were found to be associated with gender, with miR-192 being significantly upregulated in male GC patients. Kaplan-Meier analysis indicated that high expressions of exosomal miR-31, miR-375, and miR-192 were positively correlated with poor clinical outcomes of GC patients. Cox univariate and multivariate analysis found that ex-miR-375 expression and TNM stage were independent prognostic factors of overall survival (OS). Our findings revealed that exosomal miR-31, miR-192, and miR-375 might serve as noninvasive, sensitive, and specific biomarkers for the diagnosis and prognosis of GC patients.

DOI: https://doi.org/10.1155/2023/7335456