bims-exocan 2024-03-17 papers

bims-exocan

Biomed News

on Exosomes roles in cancer

Issue of 2024–03–17
nine papers selected by
Muhammad Rizwan, COMSATS University

Exosomes-Promising Carriers for Regulatory Therapy in Oncology.
Proton Treatment Suppresses Exosome Production in Head and Neck Squamous Cell Carcinoma.
Extracellular Vesicles as Novel Diagnostic and Therapeutic Agents for Non-Melanoma Skin Cancer: A Systematic Review.
Advances in 3D Culture Models to Study Exosomes in Triple-Negative Breast Cancer.
Targeted exosome-based nanoplatform for new-generation therapeutic strategies.
Exosomal ncRNAs: Multifunctional contributors to the immunosuppressive tumor microenvironment of hepatocellular carcinoma.
Unfolding the Complexity of Exosome-Cellular Interactions on Tumour Immunity and Their Clinical Prospects in Nasopharyngeal Carcinoma.
Extracellular vesicles and cancer stemness in hepatocellular carcinoma - is there a link?
Serum exosomal miR-3662 down-regulates the expression of RBMS3 to promote malignant progression and gemcitabine resistance of breast cancer cells.

Cancers (Basel). 2024 Feb 25. pii: 923. [Epub ahead of print]16(5):

Exosomes-Promising Carriers for Regulatory Therapy in Oncology.

Teresa Maria Jóźwicka, Patrycja Maria Erdmańska, Agnieszka Stachowicz-Karpińska, Magdalena Olkiewicz, Wojciech Jóźwicki.

  Extracellular vesicles (EVs), including exosomes and microvesicles, together with apoptotic bodies form a diverse group of nanoparticles that play a crucial role in intercellular communication, participate in numerous physiological and pathological processes. In the context of cancer, they can allow the transfer of bioactive molecules and genetic material between cancer cells and the surrounding stromal cells, thus promoting such processes as angiogenesis, metastasis, and immune evasion. In this article, we review recent advances in understanding how EVs, especially exosomes, influence tumor progression and modulation of the microenvironment. The key mechanisms include exosomes inducing the epithelial-mesenchymal transition, polarizing macrophages toward protumoral phenotypes, and suppressing antitumor immunity. The therapeutic potential of engineered exosomes is highlighted, including their loading with drugs, RNA therapeutics, or tumor antigens to alter the tumor microenvironment. Current techniques for their isolation, characterization, and engineering are discussed. Ongoing challenges include improving exosome loading efficiency, optimizing biodistribution, and enhancing selective cell targeting. Overall, exosomes present promising opportunities to understand tumorigenesis and develop more targeted diagnostic and therapeutic strategies by exploiting the natural intercellular communication networks in tumors. In the context of oncology, regulatory therapy provides the possibility of reproducing the original conditions that are unfavorable for the existence of the cancer process and may thus be a feasible alternative to population treatments. We also review current access to the technology enabling regulatory intervention in the cancer process using exosomes.

Keywords:  cancer regulatory therapy; engineered exosomes; exosomes; extracellular vesicles; signaling molecules

DOI:  https://doi.org/10.3390/cancers16050923
Cancers (Basel). 2024 Feb 29. pii: 1008. [Epub ahead of print]16(5):

Proton Treatment Suppresses Exosome Production in Head and Neck Squamous Cell Carcinoma.

Ameet A Chimote, Maria A Lehn, Jay Bhati, Anthony E Mascia, Mathieu Sertorio, Michael A Lamba, Dan Ionascu, Alice L Tang, Scott M Langevin, Marat V Khodoun, Trisha M Wise-Draper, Laura Conforti.

  Proton therapy (PT) is emerging as an effective and less toxic alternative to conventional X-ray-based photon therapy (XRT) for patients with advanced head and neck squamous cell carcinomas (HNSCCs) owing to its clustered dose deposition dosimetric characteristics. For optimal efficacy, cancer therapies, including PT, must elicit a robust anti-tumor response by effector and cytotoxic immune cells in the tumor microenvironment (TME). While tumor-derived exosomes contribute to immune cell suppression in the TME, information on the effects of PT on exosomes and anti-tumor immune responses in HNSCC is not known. In this study, we generated primary HNSCC cells from tumors resected from HNSCC patients, irradiated them with 5 Gy PT or XRT, and isolated exosomes from cell culture supernatants. HNSCC cells exposed to PT produced 75% fewer exosomes than XRT- and non-irradiated HNSCC cells. This effect persisted in proton-irradiated cells for up to five days. Furthermore, we observed that exosomes from proton-irradiated cells were identical in morphology and immunosuppressive effects (suppression of IFN-γ release by peripheral blood mononuclear cells) to those of photon-irradiated cells. Our results suggest that PT limits the suppressive effect of exosomes on cancer immune surveillance by reducing the production of exosomes that can inhibit immune cell function.

Keywords:  HNSCC; IFN-γ; cancer immunology; exosomes; head and neck cancers; photon therapy; proton therapy; radiation therapy

DOI:  https://doi.org/10.3390/cancers16051008
Int J Mol Sci. 2024 Feb 23. pii: 2617. [Epub ahead of print]25(5):

Extracellular Vesicles as Novel Diagnostic and Therapeutic Agents for Non-Melanoma Skin Cancer: A Systematic Review.

Konstantinos Seretis, Eleni Boptsi, Anastasia Boptsi.

  Standard non-melanoma skin cancer (NMSC) treatment involves surgery, recently combined with chemotherapy or immunotherapy in cases of advanced tumors. EVs, including exosomes, are integral to carcinogenesis, and are found in NMSC releasing mediators impacting tumor progression. Nevertheless, the precise intercellular signaling role of NMSC-derived EVs remains unclear. This review aims to elucidate their potential role in NMSC diagnosis and treatment. This systematic review encompassed literature searches in electronic databases from inception to September 2023, based on certain inclusion and exclusion criteria, addressing NMSC-derived EVs, their molecular cargo, and their implications in the diagnosis, prognosis, and treatment of NMSC. Key components were identified. Extracellular vesicle (EV) proteins and RNA have emerged as diagnostic biomarkers in EV-based liquid biopsy. Circular RNA CYP24A1, known for its molecular stability, holds promise as a diagnostic biomarker. Long noncoding RNAs (lincRNA-PICSAR) and Desmoglein 2 (DSg2) are linked to drug resistance, serving as prognostic biomarkers. EV mediators are being actively investigated for their potential role as drug delivery agents. In conclusion, this systematic review showed that NMSC-derived EVs display promise as therapeutic targets and diagnostic biomarkers. Further research is imperative to fully comprehend EV mechanisms and explore their potential in cancer diagnosis and treatment.

Keywords:  basal cell carcinoma; biomarker; cutaneous squamous cell carcinoma; diagnosis; exosomes; extracellular vesicles; non-melanoma skin cancer; prognosis; treatment

DOI:  https://doi.org/10.3390/ijms25052617
Cancers (Basel). 2024 Feb 22. pii: 883. [Epub ahead of print]16(5):

Advances in 3D Culture Models to Study Exosomes in Triple-Negative Breast Cancer.

Neelum Aziz Yousafzai, Lamyae El Khalki, Wei Wang, Justin Szpendyk, Khalid Sossey-Alaoui.

  Breast cancer, a leading cause of cancer-related deaths globally, exhibits distinct subtypes with varying pathological, genetic, and clinical characteristics. Despite advancements in breast cancer treatments, its histological and molecular heterogeneity pose a significant clinical challenge. Triple-negative breast cancer (TNBC), a highly aggressive subtype lacking targeted therapeutics, adds to the complexity of breast cancer treatment. Recent years have witnessed the development of advanced 3D culture technologies, such as organoids and spheroids, providing more representative models of healthy human tissue and various malignancies. These structures, resembling organs in structure and function, are generated from stem cells or organ-specific progenitor cells via self-organizing processes. Notably, 3D culture systems bridge the gap between 2D cultures and in vivo studies, offering a more accurate representation of in vivo tumors' characteristics. Exosomes, small nano-sized molecules secreted by breast cancer and stromal/cancer-associated fibroblast cells, have garnered significant attention. They play a crucial role in cell-to-cell communication, influencing tumor progression, invasion, and metastasis. The 3D culture environment enhances exosome efficiency compared to traditional 2D cultures, impacting the transfer of specific cargoes and therapeutic effects. Furthermore, 3D exosomes have shown promise in improving therapeutic outcomes, acting as potential vehicles for cancer treatment administration. Studies have demonstrated their role in pro-angiogenesis and their innate therapeutic potential in mimicking cellular therapies without side effects. The 3D exosome model holds potential for addressing challenges associated with drug resistance, offering insights into the mechanisms underlying multidrug resistance and serving as a platform for drug screening. This review seeks to emphasize the crucial role of 3D culture systems in studying breast cancer, especially in understanding the involvement of exosomes in cancer pathology.

Keywords:  3D culture; EMT; TNBC; breast cancer; exosomes; extracellular vesicles; immuno-oncology; metastasis; organoids; tumor microenvironment

DOI:  https://doi.org/10.3390/cancers16050883
Biomed Mater. 2024 Mar 12.

Targeted exosome-based nanoplatform for new-generation therapeutic strategies.

Wenjing Yin, Hongyin Ma, Yang Qu, Siji Wang, Ruoyu Zhao, Yi Yang, Zhen-Ni Guo.

  Exosomes, typically 30-150 nm in size, are lipid-bilayered small-membrane vesicles originating in endosomes. Exosome biogenesis is regulated by the coordination of various mechanisms whereby different cargoes (e.g., proteins, nucleic acids, and lipids) are sorted into exosomes. These components endow exosomes with bioregulatory functions related to signal transmission and intercellular communication. Exosomes exhibit substantial potential as drug-delivery nanoplatforms owing to their excellent biocompatibility and low immunogenicity. Proteins, miRNA, siRNA, mRNA, and drugs have been successfully loaded into exosomes, and these exosome-based delivery systems show satisfactory therapeutic effects in different disease models. To enable targeted drug delivery, genetic engineering and chemical modification of the lipid bilayer of exosomes are performed. Stimuli-responsive delivery nanoplatforms designed with appropriate modifications based on various stimuli allow precise control of on-demand drug delivery and can be utilized in clinical treatment. In this review, we summarize the general properties, isolation methods, characterization, biological functions, and the potential role of exosomes in therapeutic delivery systems. Moreover, the effective combination of the intrinsic advantages of exosomes and advanced bioengineering, materials science, and clinical translational technologies are required to accelerate the development of exosome-based delivery nanoplatforms.&#xD.

Keywords:  delivery; engineering; exosomes; therapeutic

DOI:  https://doi.org/10.1088/1748-605X/ad3310
Biomed Pharmacother. 2024 Mar 08. pii: S0753-3322(24)00293-2. [Epub ahead of print]173 116409

Exosomal ncRNAs: Multifunctional contributors to the immunosuppressive tumor microenvironment of hepatocellular carcinoma.

Qi Huang, Xin Zhong, Jing Li, Rui Hu, Jinyu Yi, Jialing Sun, Youhua Xu, Xiaozhou Zhou.

  Hepatocellular carcinoma (HCC) is a malignant liver cancer characterized by aggressive progression, unfavorable prognosis, and an increasing global health burden. Therapies that precisely target immunological checkpoints and immune cells have gained significant attention as possible therapeutics in recent years. In truth, the efficacy of immunotherapy is heavily contingent upon the tumor microenvironment (TME). Recent studies have indicated that exosomes serve as a sophisticated means of communication among biomolecules, executing an essential part in the TME of immune suppression. Exosomal non-coding RNAs (ncRNAs) can induce the activation of tumor cells and immunosuppressive immune cells that suppress the immune system, such as cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), CD+8 T cells, regulatory T cells (Tregs), and regulatory B cells (Bregs). This cell-cell crosstalk triggered by exosomal ncRNAs promotes tumor proliferation and metastasis, angiogenesis, malignant phenotype transformation, and drug resistance. Hence, it is imperative to comprehend how exosomal ncRNAs regulate tumor cells or immune cells within the TME to devise more comprehensive and productive immunotherapy programs. This study discusses the features of exosomal ncRNAs in HCC and how the activation of the exosomes redefines the tumor's immunosuppressive microenvironment, hence facilitating the advancement of HCC. Furthermore, we also explored the potential of exosomal ncRNAs as a viable biological target or natural vehicle for HCC therapy.

Keywords:  Exosomes; Hepatocellular carcinoma; Immunosuppression; Non-coding RNAs; Tumor microenvironment

DOI:  https://doi.org/10.1016/j.biopha.2024.116409
Cancers (Basel). 2024 Feb 24. pii: 919. [Epub ahead of print]16(5):

Unfolding the Complexity of Exosome-Cellular Interactions on Tumour Immunity and Their Clinical Prospects in Nasopharyngeal Carcinoma.

Paak-Ting Chak, Ngar-Woon Kam, Tsz-Ho Choi, Wei Dai, Dora Lai-Wan Kwong.

  Nasopharyngeal carcinoma (NPC) is an epithelial malignancy situated in the posterolateral nasopharynx. NPC poses grave concerns in Southeast Asia due to its late diagnosis. Together with resistance to standard treatment combining chemo- and radiotherapy, NPC presents high metastatic rates and common recurrence. Despite advancements in immune-checkpoint inhibitors (ICIs) and cytotoxic-T-lymphocytes (CTLs)-based cellular therapy, the exhaustive T cell profile and other signs of immunosuppression within the NPC tumour microenvironment (TME) remain as concerns to immunotherapy response. Exosomes, extracellular vesicles of 30-150 nm in diameter, are increasingly studied and linked to tumourigenesis in oncology. These bilipid-membrane-bound vesicles are packaged with a variety of signalling molecules, mediating cell-cell communications. Within the TME, exosomes can originate from tumour, immune, or stromal cells. Although there are studies on tumour-derived exosomes (TEX) in NPC and their effects on tumour processes like angiogenesis, metastasis, therapeutic resistance, there is a lack of research on their involvement in immune evasion. In this review, we aim to enhance the comprehension of how NPC TEX contribute to cellular immunosuppression. Furthermore, considering the detectability of TEX in bodily fluids, we will also discuss the potential development of TEX-related biomarkers for liquid biopsy in NPC as this could facilitate early diagnosis and prognostication of the disease.

Keywords:  biomarkers; cancer vaccine; cellular therapy; exosomes; extracellular vesicles; immune checkpoint inhibitors; liquid biopsy; nasopharyngeal carcinoma; tumour microenvironment

DOI:  https://doi.org/10.3390/cancers16050919
Front Immunol. 2024 ;15 1368898

Extracellular vesicles and cancer stemness in hepatocellular carcinoma - is there a link?

Lu Tian, Jingyi Lu, Irene Oi-Lin Ng.

  Hepatocellular carcinoma (HCC) is a highly aggressive malignancy, with high recurrence rates and notorious resistance to conventional chemotherapy. Cancer stemness refers to the stem-cell-like phenotype of cancer cells and has been recognized to play important roles in different aspects of hepatocarcinogenesis. Small extracellular vesicles (sEVs) are small membranous particles secreted by cells that can transfer bioactive molecules, such as nucleic acids, proteins, lipids, and metabolites, to neighboring or distant cells. Recent studies have highlighted the role of sEVs in modulating different aspects of the cancer stemness properties of HCC. Furthermore, sEVs derived from diverse cellular sources, such as cancer cells, stromal cells, and immune cells, contribute to the maintenance of the cancer stemness phenotype in HCC. Through cargo transfer, specific signaling pathways are activated within the recipient cells, thus promoting the stemness properties. Additionally, sEVs can govern the secretion of growth factors from non-cancer cells to further maintain their stemness features. Clinically, plasma sEVs may hold promise as potential biomarkers for HCC diagnosis and treatment prediction. Understanding the underlying mechanisms by which sEVs promote cancer stemness in HCC is crucial, as targeting sEV-mediated communication may offer novel strategies in treatment and improve patient outcome.

Keywords:  cancer associated fibroblasts (CAF); cancer stemness; extracellular vesicles; hepatocellular carcinoma; immune cells

DOI:  https://doi.org/10.3389/fimmu.2024.1368898
Chem Biol Drug Des. 2024 Mar;103(3): e14488

Serum exosomal miR-3662 down-regulates the expression of RBMS3 to promote malignant progression and gemcitabine resistance of breast cancer cells.

Xiang Li, Xu Chu, Hao Wang, Ling Xiang, Xuandi Yue.

  Breast cancer (BC) is a prevalent malignancy among women worldwide. As an anticancer drug of pyrimidine nucleoside analogs, gemcitabine can be used to treat BC, but its clinical application is restricted due to drug resistance. This study investigated the effect of serum exosomal microRNA-3662 (miR-3662) on gemcitabine resistance in BC cells by targeting RNA-Binding Motif Single-Stranded Interacting Protein 3 (RBMS3) and related molecular mechanisms. We performed the bioinformatics analyses on the differential miRNAs in BC and predicted the downstream regulators. Quantitative real-time polymerase chain reaction was conducted to determine miR-3662 and RBMS3 expression, while dual luciferase was conducted to confirme the regulatory relationship between them. Flow cytometry, cell counting kit-8, and transwell assays were applied to assess apoptosis, cell viability, invasion, and migration. The expression of marker proteins (TSG101, CD63, and CD81) in patients' serum exosomes was evaluated through western blot, and exosomes were observed using transmission electron microscopy. miR-3662 expression was significantly upregulated in BC, and miR-3662 knockdown significantly reduced BC cell viability and gemcitabine resistance. As the downstream gene of miR-3662, RBMS3 was significantly downregulated in BC, and dual luciferase assay verified the binding of RBMS3-3'UTR to miR-3662. Rescue experiments revealed that silencing RBMS3 reversed the inhibitory effect of miR-3662 knockdown on BC cells. Besides, we also found that miR-3662 expression was significantly low in serum exosome samples from BC patients and could be transmitted to tumor cells. miR-3662 was upregulated in serum exosomes and promoted BC cell progression and gemcitabine resistance by targeting RBMS3.

Keywords:  RBMS3; breast cancer cells; exosome; gemcitabine resistance; miR-3662

DOI:  https://doi.org/10.1111/cbdd.14488