bims-exocan 2024-09-08 papers

bims-exocan

Biomed News

on Exosomes roles in cancer

Issue of 2024–09–08
ten papers selected by
Muhammad Rizwan, COMSATS University

Dissecting the roles of exosomal cancer-associated fibroblasts-derived non-coding RNAs in tumor progression: A complete guide.
Exosomal misfolded proteins released by cancer stem cells: dual functions in balancing protein homeostasis and orchestrating tumor progression.
Exosomes That Have Different Cellular Origins Followed by the Impact They Have on Prostate Tumor Development in the Tumor Microenvironment.
Exosomal miR-21-5p derived from endometrial stromal cells promotes angiogenesis by targeting TIMP3 in ovarian endometrial cysts.
Role of extracellular vesicle-associated proteins in the progression, diagnosis, and treatment of hepatocellular carcinoma.
Interaction of Exosomal MicroRNA and Oxidative Stress in the Pathogenesis of Colitis-Associated Cancer.
Bladder cancer: non-coding RNAs and exosomal non-coding RNAs.
Cancer cell-derived exosome based dual-targeted drug delivery system for non-small cell lung cancer therapy.
The potential of exosomes as a new therapeutic strategy for glioblastoma.
Hydrogel encapsulation of mesenchymal stem cells-derived extracellular vesicles as a novel therapeutic approach in cancer therapy.

Pathol Res Pract. 2024 Aug 30. pii: S0344-0338(24)00487-4. [Epub ahead of print]262 155576

Dissecting the roles of exosomal cancer-associated fibroblasts-derived non-coding RNAs in tumor progression: A complete guide.

Mahnaz Farahani, Mohammad H Ghazimoradi.

  Cancer-associated fibroblasts are the most important cellular component of the tumor microenvironment, controlling cancer progression and therapeutic response. These cells in the tumor microenvironment regulate tumor progression and development as oncogenic or tumor suppressor agents. However, the mechanisms by which CAFs communicate with cancer cells remain to investigate. Here, we review evidence that extracellular vesicles, particularly exosomes, serve as vehicles for the intercellular transfer of bioactive cargos, notably microRNAs and long non-coding RNAs, from CAFs to cancer cells. We try to highlight molecular pathways of non-coding RNAs and the interaction among these molecules. Together, these findings elucidate a critical exosome-based communication axis by which CAFs create mostly a supportive pro-tumorigenic microenvironment and highlight therapeutic opportunities for disrupting this intercellular crosstalk.

Keywords:  CAF; Cancer; Cancer-associated fibroblast; Exosome; LncRNA; MiRNA; NcRNA

DOI:  https://doi.org/10.1016/j.prp.2024.155576
Discov Oncol. 2024 Aug 31. 15(1): 392

Exosomal misfolded proteins released by cancer stem cells: dual functions in balancing protein homeostasis and orchestrating tumor progression.

Anuran Bhattacharya, Urmi Chatterji.

  Cancer stem cells (CSCs), the master regulators of tumor heterogeneity and progression, exert profound influence on cancer metastasis, via various secretory vesicles. Emerging from CSCs, the exosomes serve as pivotal mediators of intercellular communication within the tumor microenvironment, modulating invasion, angiogenesis, and immune responses. Moreover, CSC-derived exosomes play a central role in sculpting a dynamic landscape, contributing to the malignant phenotype. Amidst several exosomal cargoes, misfolded proteins have recently gained attention for their dual functions in maintaining protein homeostasis and promoting tumor progression. Disrupting these communication pathways could potentially prevent the maintenance and expansion of CSCs, overcome treatment resistance, and inhibit the supportive environment created by the tumor microenvironment, thereby improving the effectiveness of cancer therapies and reducing the risk of tumor recurrence and metastasis. Additionally, exosomes have also shown potential therapeutic applications, such as in drug delivery or as biomarkers for cancer diagnosis and prognosis. Therefore, comprehending the biology of exosomes derived from CSCs is a multifaceted area of research with implications in both basic sciences and clinical applications. This review explores the intricate interplay between exosomal misfolded proteins released by CSCs, the potent contributor in tumor heterogeneity, and their impact on cellular processes, shedding light on their role in cancer progression.

Keywords:  Cancer stem cells; Drug resistance; Exosomes; Metastasis; Misfolded proteins; Proteostasis

DOI:  https://doi.org/10.1007/s12672-024-01262-z
Cancer Rep (Hoboken). 2024 Sep;7(9): e70001

Exosomes That Have Different Cellular Origins Followed by the Impact They Have on Prostate Tumor Development in the Tumor Microenvironment.

Cong Huang, Jialong Zhang, Hongzhi Wang, Chaozhao Liang.

   BACKGROUND: Prostate cancer (PCa) is the most common urinary tumor with the highest incidence rate and the second among the leading causes of death worldwide for adult males. In the worldwide cancer incidence rate, PCa is on the increase. The cancerous cells in the prostate and cells in the microenvironment surrounding the tumor communicate through signal transduction, which is crucial for the development and spread of PCa.
RECENT FINDINGS: Exosomes are nanoscale vesicles released into body fluids by various cells that can aid intercellular communication by releasing nucleic acids and proteins. Exosomes published by different types of cells in the tumor microenvironment can have varying impacts on the proliferation and growth of tumor cells via various signaling pathways, modes of action, and secreted cytokines.
CONCLUSION: The main purpose of this review is to describe the effects of different cell-derived exosomes in the tumor microenvironment of PCa on the progression of tumor cells, as well as to summarize and discuss the prospects for the application of exosomes in the treatment and diagnosis of PCa.

Keywords:  biomarkers; exosomes; intercellular communication; prostate cancer; prostate cancer cells; tumor microenvironment

DOI:  https://doi.org/10.1002/cnr2.70001
J Mol Med (Berl). 2024 Sep 04.

Exosomal miR-21-5p derived from endometrial stromal cells promotes angiogenesis by targeting TIMP3 in ovarian endometrial cysts.

Liyuan Sun, Yan Cheng, Jing Wang, Di Wu, Lin Yuan, Xiaoyu Wei, Yan Li, Jie Gao, Guangmei Zhang.

  Endometriosis is a multifactorial gynecological disease, with angiogenesis as a key hallmark. The role of exosomal microRNAs (miRNAs) in endometriosis is not well understood. This study investigates differentially expressed exosomal miRNAs linked to angiogenesis in endometriosis, clarifies their molecular mechanisms, and identifies potential targets. Primary endometrial stromal cells (ESCs) were cultured, and exosomes were extracted. In a co-culture system, ESC-derived exosomes were taken up by human umbilical vein endothelial cells (HUVECs). Endometriosis implant-ESC-derived exosomes (EI-EXOs) significantly promoted HUVEC proliferation, migration and tube formation compared to normal endometrium-exosomes (NE-EXOs), a finding consistent in vivo in mice. MiRNA sequencing and bioinformatics identified differentially expressed miR-21-5p from EI-EXOs, confirmed by RT-qPCR. The miR-21-5p inhibitor or GW4869 attenuated EI-EXO-induced HUVEC proliferation, migration, and tube formation. TIMP3 overexpression diminished the pro-angiogenic effect of EI-EXOs, which was reversed by adding EI-EXOs or upregulating miR-21-5p. These findings validate the crosstalk between ESCs and HUVECs mediated by exosomal miR-21-5p, and confirm the miR-21-5p-TIMP3 axis in promoting angiogenesis in endometriosis. KEY MESSAGES: ESC-derived exosomes were found to be taken up by recipient cells, i.e. HUVECs. Functionally, endometriosis implant-ESC-derived exosomes (EI-EXOs) could significantly promote the proliferation, migration and tube formation of HUVECs compared to normal endometrium-exosomes (NE-EXOs). Through miRNA sequencing and bioinformatics analysis, differentially expressed miR-21-5p released by EI-EXOs was chosen, as confirmed by qRT-PCR. miR-21-5p inhibitor or GW4869 was found to attenuate the proliferation, migration, and tube formation of HUVECs induced by EI-EXOs. In turn, TIMP3 overexpression diminished the pro-angiogenic effect of EI-EXOs, and this angiogenic phenotype was reversed once EI-EXOs were added or miR-21-5p was upregulated.

Keywords:  Angiogenesis; Endometrial stromal cells; Endometriosis; Exosomes, miR-21-5p; HUVECs; TIMP3

DOI:  https://doi.org/10.1007/s00109-024-02483-z
Cell Biosci. 2024 Sep 03. 14(1): 113

Role of extracellular vesicle-associated proteins in the progression, diagnosis, and treatment of hepatocellular carcinoma.

Yao-Ge Liu, Shi-Tao Jiang, Jun-Wei Zhang, Han Zheng, Lei Zhang, Hai-Tao Zhao, Xin-Ting Sang, Yi-Yao Xu, Xin Lu.

  Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, characterized by difficulties in early diagnosis, prone to distant metastasis, and high recurrence rates following surgery. Extracellular vesicles (EVs) are a class of cell-derived particles, including exosomes, characterized by a phospholipid bilayer. They serve as effective carriers for intercellular communication cargo, including proteins and nucleic acids, and are widely involved in tumor progression. They are being explored as potential tumor biomarkers and novel therapeutic avenues. We provide a brief overview of the biogenesis and characteristics of EVs to better understand their classification standards. The focus of this review is on the research progress of EV-associated proteins in the field of HCC. EV-associated proteins are involved in tumor growth and regulation in HCC, participate in intercellular communication within the tumor microenvironment (TME), and are implicated in events including angiogenesis and epithelial-mesenchymal transition (EMT) during tumor metastasis. In addition, EV-associated proteins show promising diagnostic efficacy for HCC. For the treatment of HCC, they also demonstrate significant potential including enhancing the efficacy of tumor vaccines, and as targeting cargo anchors. Facing current challenges, we propose the future directions of research in this field. Above all, research on EV-associated proteins offers the potential to enhance our comprehension of HCC and offer novel insights for developing new treatment strategies.

Keywords:  Biomarkers; EV-associated proteins; Extracellular vesicles (EVs); Hepatocellular carcinoma (HCC); Proteomics; Tumor microenvironment (TME)

DOI:  https://doi.org/10.1186/s13578-024-01294-6
Front Biosci (Landmark Ed). 2024 Aug 07. 29(8): 276

Interaction of Exosomal MicroRNA and Oxidative Stress in the Pathogenesis of Colitis-Associated Cancer.

Yifan Li, Huanyu Li, Manli Cui, Ying Zhou, Mingzhen Zhang, Mingxin Zhang.

  Colitis-associated cancer (CAC) is the most serious complication of inflammatory bowel disease. In recent years, the incidence of CAC has increased worldwide. Oxidative stress (OS) is involved in the development of CAC through oxidative damage to biomolecules or activation of inflammatory signaling pathways. Exosomes are extracellular vesicles that act as messengers to deliver signals and macromolecules to target cells, making them important mediators of intercellular communication and exchange of biologically active molecules between cells. MicroRNAs (miRNAs) carried by exosomes regulate the pro- and anti-inflammatory pathways of OS and play a key role in communication between OS and cancer cells. This review describes the correlation between OS and exosomal miRNAs with the goal of identifying a novel therapeutic method for CAC.

Keywords:  colitis-associated cancer; exosome microRNAs; oxidative stress

DOI:  https://doi.org/10.31083/j.fbl2908276
Funct Integr Genomics. 2024 Aug 31. 24(5): 147

Bladder cancer: non-coding RNAs and exosomal non-coding RNAs.

Jingang Zhao, Yangyang Ma, Xiaodong Zheng, Zhen Sun, Hongxiang Lin, Chuanjun Du, Jing Cao.

  Bladder cancer (BCa) is a highly prevalent type of cancer worldwide, and it is responsible for numerous deaths and cases of disease. Due to the diverse nature of this disease, it is necessary to conduct significant research that delves deeper into the molecular aspects, to potentially discover novel diagnostic and therapeutic approaches. Lately, there has been a significant increase in the focus on non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), due to their growing recognition for their involvement in the progression and manifestation of BCa. The interest in exosomes has greatly grown due to their potential for transporting a diverse array of active substances, including proteins, nucleic acids, carbohydrates, and lipids. The combination of these components differs based on the specific cell and its condition. Research indicates that using exosomes could have considerable advantages in identifying and forecasting BCa, offering a less invasive alternative. The distinctive arrangement of the lipid bilayer membrane found in exosomes is what makes them particularly effective for administering treatments aimed at managing cancer. In this review, we have tried to summarize different ncRNAs that are involved in BCa pathogenesis. Moreover, we highlighted the role of exosomal ncRNAs in BCa.

Keywords:  Bladder cancer; Circular RNA; Exosome; Long non-coding RNA; MicroRNA; Non-coding RNAs

DOI:  https://doi.org/10.1007/s10142-024-01433-9
Colloids Surf B Biointerfaces. 2024 Aug 05. pii: S0927-7765(24)00400-4. [Epub ahead of print]244 114141

Cancer cell-derived exosome based dual-targeted drug delivery system for non-small cell lung cancer therapy.

Jun Wang, Xinyi Zhu, Huijun Jiang, Minghui Ji, Yuan Wu, Jin Chen.

  Lung cancer is among most prevalent cancers in the world, in which non-small cell lung cancer (NSCLC) accounts for more than 85 % of all subtypes of lung cancers. NSCLC is often diagnosed at an advanced stage with a high mortality rate. Despite the demonstrated efficacy of chemotherapy in the treatment of NSCLC, the main drawback of current therapy is the lack of an effective drug-targeted delivery system, which may result in undesirable side effects during the clinical treatment. In this study, we construct a "dual-targeting" anti-cancer drug delivery platform by combining superparamagnetic iron oxide nanoparticles (SPIONs) with exosomes derived from NSCLC cells. We successfully promoted the targeted delivery of anti-drug doxorubicin (DOX) at the cellular levels by combining the homing targeted ability of exosomes with the magnetic targeted ability of SPIONs. Moreover, non-small cell lung cancer cell (NCI-h1299) tumor models were established. It was found that exosome-SPIONs (Exo-SPIONs) loaded with DOX exhibited optimal tumor tissue delivery and tumor suppression in the presence of an external magnetic field, and reduced the toxicity of the DOX to normal tissues. The constructed "dual-targeting" anti-cancer drug delivery platform holds promise for targeted chemotherapy for NSCLC.

Keywords:  Exosome; Nanoparticles; Non-small cell lung cancer; Superparamagnetic iron oxide; Targeted delivery

DOI:  https://doi.org/10.1016/j.colsurfb.2024.114141
Eur J Pharm Biopharm. 2024 Aug 30. pii: S0939-6411(24)00286-8. [Epub ahead of print] 114460

The potential of exosomes as a new therapeutic strategy for glioblastoma.

Leonor Cunha Silva, Francisco Branco, Joana Cunha, Carla Vitorino, Célia Gomes, Mylène A Carrascal, Amílcar Falcão, Bruno Miguel Neves, Maria Teresa Cruz.

  Glioblastoma (GBM) stands for the most common and aggressive type of brain tumour in adults. It is highly invasive, which explains its short rate of survival. Little is known about its risk factors, and current therapy is still ineffective. Hence, efforts are underway to develop novel and effective treatment approaches against this type of cancer. Exosomes are being explored as a promising strategy for conveying and delivering therapeutic cargo to GBM cells. They can fuse with the GBM cell membrane and, consequently, serve as delivery systems in this context. Due to their nanoscale size, exosomes can cross the blood-brain barrier (BBB), which constitutes a significant hurdle to most chemotherapeutic drugs used against GBM. They can subsequently inhibit oncogenes, activate tumour suppressor genes, induce immune responses, and control cell growth. However, despite representing a promising tool for the treatment of GBM, further research and clinical studies regarding exosome biology, engineering, and clinical applications still need to be completed. Here, we sought to review the application of exosomes in the treatment of GBM through an in-depth analysis of the scientific and clinical studies on the entire process, from the isolation and purification of exosomes to their design and transformation into anti-oncogenic drug delivery systems. Surface modification of exosomes to enhance BBB penetration and GBM-cell targeting is also a topic of discussion.

Keywords:  Biomimetic; Cancer treatment; Delivery system; Exosomes; Gene therapy; Glioblastoma; Surface modification

DOI:  https://doi.org/10.1016/j.ejpb.2024.114460
Biochim Biophys Acta Rev Cancer. 2024 Aug 30. pii: S0304-419X(24)00108-2. [Epub ahead of print]1879(5): 189177

Hydrogel encapsulation of mesenchymal stem cells-derived extracellular vesicles as a novel therapeutic approach in cancer therapy.

Raheleh Farahzadi, Ezzatollah Fathi, Somayeh Vandghanooni, Behnaz Valipour.

  Cell therapy has emerged as one of the most promising approaches to treating disease in recent decades. The application of stem cells in anti-tumor therapy is determined by their varying capacity for proliferation, migration, and differentiation. These capacities are derived from different sources. The use of stem cell carriers in cancer treatment is justified by the following three reasons: (I) shield therapeutic agents from swift biological deterioration; (II) reduce systemic side effects; and (III) increase local therapeutic levels since stem cells have an innate ability to target tumors. The quantity of stem cells confined to the tumor microenvironment determines this system's anti-tumor activity. Nevertheless, there are limitations to the use of different types of stem cells. When immune cells are used in cell therapy, it may lead to cytokine storms and improper reactions to self-antigens. Furthermore, the use of stem cells may result in cancer. Additionally, after an intravenous injection, cells could not migrate to the injury location. Exosomes derived from different cells were thus proposed as possible therapeutic options. Exosomes are becoming more and more well-liked because of their small size, biocompatibility, and simplicity in storage and separation. A number of investigations have shown that adding various medications and microRNAs to exosomes may enhance their therapeutic effectiveness. Thus, it is essential to evaluate studies looking into the therapeutic effectiveness of encapsulated exosomes. In this review, we looked at studies on encapsulated exosomes' use in regenerative medicine and the treatment of cancer. The results imply that the therapeutic potential increases when encapsulated exosomes are used rather than intact exosomes. Therefore, in order to optimize the effectiveness of the treatment, it is advised to implement this technique in accordance with the kind of therapy.

Keywords:  Cancer therapy; Encapsulation; Hydrogel; Mesenchymal stem cells; Mesenchymal stem cells-derived exosomes

DOI:  https://doi.org/10.1016/j.bbcan.2024.189177