bims-exocan 2024-08-18 papers

bims-exocan

Biomed News

on Exosomes roles in cancer

Issue of 2024‒08‒18
nine papers selected by
Muhammad Rizwan, COMSATS University

Exosomes in Renal Cell Cancer: Diagnostic and Therapeutic Nanovehicles.
Growth Hormone Upregulates Melanoma Drug Resistance and Migration via Melanoma-Derived Exosomes.
Drug delivery based exosomes uptake pathways.
Tumor-exosomal miR-205-5p as a diagnostic biomarker for colorectal cancer.
Role of exosomal non‑coding RNAs in ovarian cancer (Review).
Exosomes: a significant medium for regulating drug resistance through cargo delivery.
Tumor-derived exosomal ICAM1 promotes bone metastasis of triple-negative breast cancer by inducing CD8+ T cell exhaustion.
Composition, functions, and applications of exosomal membrane proteins.
COL6A3 Exosomes Promote Tumor Dissemination and Metastasis in Epithelial Ovarian Cancer.

Technol Cancer Res Treat. 2024 Jan-Dec;23:23 15330338241275403

Exosomes in Renal Cell Cancer: Diagnostic and Therapeutic Nanovehicles.

Stergios Boussios, Saak V Ovsepian.

  Early diagnosis is crucial for enhancing the survival rate of renal cell cancer patients, and exosomes present potential advantages in this area. Their small size, high mobility, and lipid bilayer structure enable exosomes to cross biological membranes easily, protecting the bioactive cargo within from degradation. Exosomes significantly influence the invasion and metastasis of RCC, and they also contribute to tumor drug resistance and immune evasion.

Keywords:  Exosomes; biomarker; extracellular vesicles; renal cancer; tumor microenvironment

DOI:  https://doi.org/10.1177/15330338241275403
Cancers (Basel). 2024 Jul 24. pii: 2636. [Epub ahead of print]16(15):

Growth Hormone Upregulates Melanoma Drug Resistance and Migration via Melanoma-Derived Exosomes.

Prateek Kulkarni, Reetobrata Basu, Taylor Bonn, Beckham Low, Nathaniel Mazurek, John J Kopchick.

  Drug resistance in melanoma is a major hindrance in cancer therapy. Growth hormone (GH) plays a pivotal role in contributing to the resistance to chemotherapy. Knocking down or blocking the GH receptor has been shown to sensitize the tumor cells to chemotherapy. Extensive studies have demonstrated that exosomes, a subset of extracellular vesicles, play an important role in drug resistance by transferring key factors to sensitize cancer cells to chemotherapy. In this study, we explore how GH modulates exosomal cargoes from melanoma cells and their role in drug resistance. We treated the melanoma cells with GH, doxorubicin, and the GHR antagonist, pegvisomant, and analyzed the exosomes released. Additionally, we administered these exosomes to the recipient cells. The GH-treated melanoma cells released exosomes with elevated levels of ABC transporters (ABCC1 and ABCB1), N-cadherin, and MMP2, enhancing drug resistance and migration in the recipient cells. GHR antagonism reduced these exosomal levels, restoring drug sensitivity and attenuating migration. Overall, our findings highlight a novel role of GH in modulating exosomal cargoes that drive chemoresistance and metastasis in melanoma. This understanding provides insights into the mechanisms of GH in melanoma chemoresistance and suggests GHR antagonism as a potential therapy to overcome chemoresistance in melanoma treatment.

Keywords:  ABC transporters; MMP2; N-cadherin; chemotherapy resistance; exosomes; growth hormone; melanoma; pegvisomant

DOI:  https://doi.org/10.3390/cancers16152636
Neurochem Int. 2024 Aug 13. pii: S0197-0186(24)00162-1. [Epub ahead of print]179 105835

Drug delivery based exosomes uptake pathways.

Moataz Dowaidar.

  Most cells secrete a material called extracellular vesicles (EVs), which play a crucial role in cellular communication. Exosomes are one of the most studied types of EVs. Recent research has shown the many functions and substrates of cellular exosomes. Multiple studies have shown the efficacy of exosomes in transporting a wide variety of cargo to their respective target cells. As a result, they are often utilized to transport medicaments to patients. Natural exosomes as well as exosomes modified with other compounds to enhance transport capabilities have been employed. In this article, we take a look at how different types of exosomes and modified exosomes may transport different types of cargo to their respective targets. Exosomes have a lot of potential as drug delivery vehicles for many synthetic compounds, proteins, nucleic acids, and gene repair specialists because they can stay in the body for a long time, are biocompatible, and can carry natural materials. A good way to put specific protein particles into exosomes is still not clear, though, and the exosomes can't be used in many situations yet. The determinants for exosome production, as well as ways for loading certain therapeutic molecules (proteins, nucleic acids, and small compounds), were covered in this paper. Further study and the development of therapeutic exosomes may both benefit from the information collected in this review.

Keywords:  Delivery properties; Drug carrier; Exosome; Extracellular vesicles; Therapeutic strategy

DOI:  https://doi.org/10.1016/j.neuint.2024.105835
Clin Transl Oncol. 2024 Aug 12.

Tumor-exosomal miR-205-5p as a diagnostic biomarker for colorectal cancer.

Yajing Zhao, Yapeng Zhao, Lisheng Liu, Guanghao Li, Yawen Wu, Yanan Cui, Li Xie.

  BACKGROUND: Tumor-derived exosomal miRNAs play crucial roles in cancer diagnosis. Current studies aim to identify exosomal miRNAs associated with colorectal cancer (CRC) that are noninvasive, sensitive, and specific.PATIENTS AND METHODS: Exosomes were extracted from CRC patients and healthy donors via ultracentrifugation, followed by verification via transmission electron microscopy (TEM), qNano, and Western blot analysis. The differential expression levels and clinical characteristics of miR-205-5p were analyzed in CRC via data from The Cancer Genome Atlas (TCGA). Real-time quantitative PCR was used to assess the expression levels of exosomal miRNAs in 157 primary CRC patients, 20 patients with benign diseases, and 135 healthy donors. Predictions regarding target genes were made to guide further exploration of the disease's etiopathogenesis through bioinformatics.
RESULTS: Compared with that in healthy donors, the expression of miR-205-5p in colorectal cancer (CRC) patients was significantly lower, as determined through analysis of the TCGA database. We conducted a prediction and analysis of the functional enrichment of downstream target genes regulated by miR-205-5p. A lower level of exosomal miR-205-5p in the serum of CRC patients than in that of healthy controls (p < 0.0001) and patients with benign disease (p < 0.0001) was observed. Furthermore, the expression levels of exosomal miR-205-5p were significantly lower in early-stage CRC patients than in the comparison groups (p<0.001 and p < 0.0001). Notably, the expression levels of exosomal miR-205-5p significantly increased postoperatively (p = 0.0053).
CONCLUSIONS: The present study demonstrated that serum exosomal miR-205-5p may be a diagnostic biomarker for CRC.

Keywords:  Colorectal cancer; Diagnosis; Exosomes; miR-205-5p

DOI:  https://doi.org/10.1007/s12094-024-03647-6
Int J Mol Med. 2024 Oct;pii: 87. [Epub ahead of print]54(4):

Role of exosomal non‑coding RNAs in ovarian cancer (Review).

Xinchen Wang, Miao Yang, Jiamei Zhu, Yu Zhou, Gencui Li.

  Ovarian cancer (OC) is a common gynecological disease with a high mortality rate worldwide due to its insidious nature and undetectability at an early stage. The standard treatment, combining platinum‑based chemotherapy with cytoreductive surgery, has suboptimal results. Therefore, early diagnosis of OC is crucial. All cell types secrete extracellular vesicles, particularly exosomes. Exosomes, which contain lipids, proteins, DNA and non‑coding RNAs (ncRNAs), are novel methods of intercellular communication that participate in tumor development and progression. ncRNAs are categorized by size into long ncRNAs (lncRNAs) and small ncRNAs (sncRNAs). sncRNAs further include transfer RNAs, small nucleolar RNAs, PIWI‑interacting RNAs and microRNAs (miRNAs). miRNAs inhibit protein translation and promote messenger RNA (mRNA) cleavage to suppress gene expression. By sponging downstream miRNAs, lncRNAs and circular RNAs can regulate target gene expression, thereby weakening the interactions between miRNAs and mRNAs. Exosomes and exosomal ncRNAs, commonly present in human biological fluids, are promising biomarkers for OC. The present article aimed to review the potential role of exosomal ncRNAs in the diagnosis and prognosis of OC by summarizing the characteristics, processes, roles and isolation methods of exosomes and exosomal ncRNAs.

Keywords:  biomarkers; circular RNA; exosomal non‑coding RNA; long non‑coding RNA; microRNA; ovarian cancer

DOI:  https://doi.org/10.3892/ijmm.2024.5411
Front Mol Biosci. 2024 ;11 1379822

Exosomes: a significant medium for regulating drug resistance through cargo delivery.

Bixuan Ren, Xiaoqing Li, Zhihua Zhang, Sheng Tai, Shan Yu.

  Exosomes are small lipid nanovesicles with a diameter of 30-150 nm. They are present in all body fluids and are actively secreted by the majority of cells through the process of exocytosis. Exosomes play an essential role in intercellular communication and act as significant molecular carriers in regulating various physiological and pathological processes, such as the emergence of drug resistance in tumors. Tumor-associated exosomes transfer drug resistance to other tumor cells by releasing substances such as multidrug resistance proteins and miRNAs through exosomes. These substances change the cell phenotype, making it resistant to drugs. Tumor-associated exosomes also play a role in impacting drug resistance in other cells, like immune cells and stromal cells. Exosomes alter the behavior and function of these cells to help tumor cells evade immune surveillance and form a tumor niche. In addition, exosomes also export substances such as tumoricidal drugs and neutralizing antibody drugs to help tumor cells resist drug therapy. In this review, we summarize the mechanisms of exosomes in promoting drug resistance by delivering cargo in the context of the tumor microenvironment (TME).

Keywords:  drug resistance; exosomes; immune escape; tumor; tumor environment

DOI:  https://doi.org/10.3389/fmolb.2024.1379822
Int J Biochem Cell Biol. 2024 Aug 13. pii: S1357-2725(24)00129-8. [Epub ahead of print] 106637

Tumor-derived exosomal ICAM1 promotes bone metastasis of triple-negative breast cancer by inducing CD8+ T cell exhaustion.

Mingcang Chen, Zhengwei Fu, Chunyu Wu.

  Exosomes, which are nanosized extracellular vesicles, have emerged as crucial mediators of the crosstalk between tumor cells and the immune system. Intercellular adhesion molecule 1 (ICAM1) plays a crucial role in multiple immune functions as well as in the occurrence, development and metastasis of cancer. As a glycoprotein expressed on the cell membrane, ICAM1 is secreted extracellularly on exosomes and regulates the immunosuppressive microenvironment. However, the role of exosomal ICAM1 in the immune microenvironment of breast cancer bone metastases remains unclear. This study aimed to elucidated the role of exosomal ICAM1 in facilitating CD8+ T cell exhaustion and subsequent bone metastasis in triple-negative breast cancer (TNBC). We demonstrated that TNBC cells release ICAM1-enriched exosomes, and the binding of ICAM1 to its receptor is necessary for the suppressive effect of CD8 T cell proliferation and function. This pivotal engagement not only inhibits CD8+ T cell proliferation and activation but also initiates the development of an immunosuppressive microenvironment that is conducive to TNBC tumor growth and bone metastasis. Moreover, ICAM1 blockade significantly impairs the ability of tumor exosomes to bind to CD8+ T cells, thereby inhibiting their immunosuppressive effects. The present study elucidates the complex interaction between primary tumors and the immune system that is mediated by exosomes and provides a foundation for the development of novel cancer immunotherapies that target ICAM1 with the aim of mitigating TNBC bone metastasis.

Keywords:  CD8+ T cell exhaustion; Exosomes; ICAM1; PD-L1; TNBC; bone metastasis; immunotherapy

DOI:  https://doi.org/10.1016/j.biocel.2024.106637
Front Immunol. 2024 ;15 1408415

Composition, functions, and applications of exosomal membrane proteins.

Fang Xu, Shumin Luo, Pengpeng Lu, Chao Cai, Weihua Li, Chuanyun Li.

  Exosomes play a crucial role in various biological processes, such as human development, immune responses, and disease occurrence. The membrane proteins on exosomes are pivotal factors for their biological functionality. Currently, numerous membrane proteins have been identified on exosome membranes, participating in intercellular communication, mediating target cell recognition, and regulating immune processes. Furthermore, membrane proteins from exosomes derived from cancer cells can serve as relevant biomarkers for early cancer diagnosis. This article provides a comprehensive review of the composition of exosome membrane proteins and their diverse functions in the organism's biological processes. Through in-depth exploration of exosome membrane proteins, it is expected to offer essential foundations for the future development of novel biomedical diagnostics and therapies.

Keywords:  applications; exosomes; functions; immunoregulation; membrane proteins

DOI:  https://doi.org/10.3389/fimmu.2024.1408415
Int J Mol Sci. 2024 Jul 25. pii: 8121. [Epub ahead of print]25(15):

COL6A3 Exosomes Promote Tumor Dissemination and Metastasis in Epithelial Ovarian Cancer.

Chih-Ming Ho, Ting-Lin Yen, Tzu-Hao Chang, Shih-Hung Huang.

  Our study explores the role of cancer-derived extracellular exosomes (EXs), particularly focusing on collagen alpha-3 (VI; COL6A3), in facilitating tumor dissemination and metastasis in epithelial ovarian cancer (EOC). We found that COL6A3 is expressed in aggressive ES2 derivatives, SKOV3 overexpressing COL6A3 (SKOV3/COL6A3), and mesenchymal-type ovarian carcinoma stromal progenitor cells (MSC-OCSPCs), as well as their EXs, but not in less aggressive SKOV3 cells or ES2 cells with COL6A3 knockdown (ES2/shCOL6A3). High COL6A3 expression correlates with worse overall survival among EOC patients, as evidenced by TCGA and GEO data analysis. In vitro experiments showed that EXs from MSC-OCSPCs or SKOV3/COL6A3 cells significantly enhance invasion ability in ES2 or SKOV3/COL6A3 cells, respectively (both, p <0.001). In contrast, ES2 cells with ES2/shCOL6A3 EXs exhibited reduced invasion ability (p < 0.001). In vivo, the average disseminated tumor numbers in the peritoneal cavity were significantly greater in mice receiving intraperitoneally injected SKOV3/COL6A3 cells than in SKOV3 cells (p < 0.001). Furthermore, mice intravenously (IV) injected with SKOV3/COL6A3 cells and SKOV3/COL6A3-EXs showed increased lung colonization compared to mice injected with SKOV3 cells and PBS (p = 0.007) or SKOV3/COL6A3 cells and PBS (p = 0.039). Knockdown of COL6A3 or treatment with EX inhibitor GW4869 or rapamycin-abolished COL6A3-EXs may suppress the aggressiveness of EOC.

Keywords:  COL6A3; aggressiveness; epithelial ovarian cancer; exosome inhibitor; exosomes; metastasis

DOI:  https://doi.org/10.3390/ijms25158121