bims-exocan 2024-12-22 papers

bims-exocan

Biomed News

on Exosomes roles in cancer

Issue of 2024–12–22
nine papers selected by
Muhammad Rizwan, COMSATS University

Exosomes as a Therapeutic Strategy in Cancer: Potential Roles as Drug Carriers and Immune Modulators.
Exosomal signaling in gynecologic cancer development: The role of cancer-associated fibroblasts.
Exosomes and breast cancer angiogenesis; Highlights in intercellular communication.
Exosomal miR-184 facilitates bladder cancer progression by targeting AKR1C3 and inducing immune escape via IRF2-CXCL10 axis.
Influence of head and neck cancer exosomes on macrophage polarization.
Biogenesis and functional implications of extracellular vesicles in cancer metastasis.
Exosomal miR-320d promotes angiogenesis and colorectal cancer metastasis via targeting GNAI1 to affect the JAK2/STAT3 signaling pathway.
Potential Use of Exosomal Non-Coding MicroRNAs in Leukemia Therapy: A Systematic Review.
Glioma-Derived Exosomes and Their Application as Drug Nanoparticles.

Biochim Biophys Acta Rev Cancer. 2024 Dec 16. pii: S0304-419X(24)00169-0. [Epub ahead of print]1880(1): 189238

Exosomes as a Therapeutic Strategy in Cancer: Potential Roles as Drug Carriers and Immune Modulators.

Azam Abedi, Mehrdad Moosazadeh Moghaddam, Reza Kachuei, Abbas Ali Imani Fooladi.

  Exosome-based cancer immunotherapy is advancing quickly on the concept of artificially activating the immune system to combat cancer. They can mechanistically change the tumor microenvironment, increase immune responses, and function as efficient drug delivery vehicles because of their inherent bioactivity, low toxicity, and immunogenicity. Accurate identification of the mechanisms of action of exosomes in tumor environments, along with optimization of their isolation, purification, and characterization methods, is necessary to increase clinical applications. Exosomes can be modified through cargo loading and surface modification to enhance their therapeutic applications, either before or after the donor cells' isolation. These engineered exosomes can directly target tumor cells at the tumor site or indirectly activate innate and adaptive immune responses in the tumor microenvironment. This approach is particularly effective when combined with traditional cancer immunotherapy techniques such as vaccines, immune checkpoints, and CAR-T cells. It can improve anti-tumor responses, induce long-term immunity, and address the limitations of traditional therapies, such as poor penetration in solid tumors and immunosuppressive environments. This review aims to provide a comprehensive and detailed overview of the direct role of engineered exosomes as drug delivery systems and their immunomodulatory effects on tumors as an indirect approach to fighting cancer. Additionally, it will discuss novel immunotherapy options.

Keywords:  CAR-T; Cancer immunotherapy; Direct/indirect effects; Exosome engineering; Immune checkpoint; Vaccination

DOI:  https://doi.org/10.1016/j.bbcan.2024.189238
Pathol Res Pract. 2024 Dec 10. pii: S0344-0338(24)00677-0. [Epub ahead of print]266 155766

Exosomal signaling in gynecologic cancer development: The role of cancer-associated fibroblasts.

Mohamed J Saadh, Omer Qutaiba B Allela, Radhwan Abdul Kareem, Muktesh Chandra, H Malathi, Deepak Nathiya, Ish Kapila, Hayder Naji Sameer, Atheer Khdyair Hamad, Zainab H Athab, Mohaned Adil.

  Gynecologic cancer, a prevalent and debilitating disease affecting women worldwide, is characterized by the uncontrolled proliferation of cells in the reproductive organs. The complex etiology of gynecologic cancer encompasses multiple subtypes, including cervical, ovarian, uterine, vaginal, and vulvar cancers. Despite optimal treatment strategies, which typically involve cytoreductive surgery and platinum-based chemotherapy, gynecologic cancer frequently exhibits recalcitrant relapse and poor prognosis. Recent studies have underscored the significance of the tumor microenvironment in ovarian carcinogenesis, particularly with regards to the discovery of aberrant genomic, transcriptomic, and proteomic profiles. Within this context, cancer-associated fibroblasts (CAFs) emerge as a crucial component of the stromal cell population, playing a pivotal role in oncogenesis and cancer progression. CAF-derived exosomes, small extracellular vesicles capable of conveying biological information between cells, have been implicated in a range of tumor-related processes, including tumorigenesis, cell proliferation, metastasis, drug resistance, and immune responses. Furthermore, aberrant expression of CAF-derived exosomal noncoding RNAs and proteins has been found to strongly correlate with clinical and pathological characteristics of gynecologic cancer patients. Our review provides a novel perspective on the role of CAF-derived exosomes in gynecologic cancer, highlighting their potential as diagnostic biomarkers and therapeutic targets.

Keywords:  Cancer-associated fibroblasts (CAFs); Exosomes; Gynecologic cancer; Tumor microenvironment

DOI:  https://doi.org/10.1016/j.prp.2024.155766
Cancer Cell Int. 2024 Dec 18. 24(1): 402

Exosomes and breast cancer angiogenesis; Highlights in intercellular communication.

Parisa Khanicheragh, Zahra Abbasi-Malati, Solmaz Saghebasl, Parisa Hassanpour, Soheil Zamen Milani, Reza Rahbarghazi, Akbar Hasani.

  Breast cancer (BC) is a prevalent and highly lethal cancer in females. Like other cancer types, the intricate cellular and molecular heterogeneity leads to the variation of therapeutic outcomes. The development and progression of blood vessels increase the tumor cell expansion and metastasis to remote sites. Based on several pieces of scientific data, different mediators and cells are involved in the promotion of angiogenesis into the tumor parenchyma. Recent data have indicated the critical role of extracellular vesicles, especially exosomes (Exos), in the transfer of angiogenesis molecules between the BC cells. Due to unique physicochemical properties, and the transfer of certain signaling molecules, Exos are at the center of attention in terms of biomarkers and therapeutic bullets in cancer patients. Along with these statements, understanding the modulatory role of Exos in BC angiogenesis seems critical in the clinical setting. Here, the mechanisms by which BC cells can orchestrate the angiogenesis phenomenon via Exos are discussed in detail. The present study can help us to understand the pro-/anti-angiogenesis role of Exos in BC and to design better oncostatic strategies.

Keywords:  Angiogenesis; Breast cancer; Exosomes; Extracellular vesicles; Paracrine communication

DOI:  https://doi.org/10.1186/s12935-024-03606-9
Biochim Biophys Acta Mol Basis Dis. 2024 Dec 15. pii: S0925-4439(24)00621-5. [Epub ahead of print] 167627

Exosomal miR-184 facilitates bladder cancer progression by targeting AKR1C3 and inducing immune escape via IRF2-CXCL10 axis.

Wenwei Ying, Ying Zhao, Yuhui He, Yisen Deng, Xiaoming Gan, Peizhe Li, Xing Chen, Zhenshan Ding.

  Currently, the molecular mechanisms underlying bladder cancer progression remain unclear. Immune checkpoint inhibitors (ICIs) have been used to treat bladder cancer, but their efficacy is limited. Exosomes, which play a critical role in cell communication, can alter the tumor microenvironment. Therefore, it is essential to investigate the impact of bladder cancer exosomes on the tumor microenvironment. Our research demonstrates a significant up-regulation of miR-184 in exosomes derived from bladder cancer cells. miR-184 promotes bladder cancer cell proliferation in vitro and facilitates tumor growth in mice by targeting the 3' UTR of AKR1C3 mRNA. Additionally, miR-184 targets IRF2 mRNA, reducing its transcriptional inhibition on CXCL10. This process induces the expression of CXCL10, which promotes the infiltration of CD8+ T cells into the tumor. However, these infiltrating T cells become exhausted. In summary, our study reveals that bladder cancer-derived exosomes deliver miR-184, which targets AKR1C3, contributing to bladder carcinogenesis and development. We also investigate how the IRF2-CXCL10 pathway induces T cell exhaustion and leads to immune escape. This research provides new insights into the immunotherapy of bladder cancer, highlighting potential molecular targets for more effective treatment strategies.

Keywords:  AKR1C3; Bladder cancer; CD8 + T cell; Extracellular vesicles; IRF2; T cell exhaustion

DOI:  https://doi.org/10.1016/j.bbadis.2024.167627
Cytokine. 2024 Dec 18. pii: S1043-4666(24)00335-1. [Epub ahead of print]186 156831

Influence of head and neck cancer exosomes on macrophage polarization.

Joni Yadav, Tanya Tripathi, Apoorva Chaudhary, Divya Janjua, Udit Joshi, Nikita Aggarwal, Arun Chhokar, Chetkar Chandra Keshavam, Anna Senrung, Alok Chandra Bharti.

   BACKGROUND: Tumor cells within the tumor microenvironment (TME) release exosomes that influence macrophage phenotypes, either pro-tumorigenic or anti-tumorigenic. This mechanism, especially in head and neck squamous cell carcinoma (HNSCC), remains poorly understood. This study investigates the role of HNSCC exosomes in macrophage polarization.
METHODOLOGY: Exosomes were isolated from HPV16-positive (93VU147T, UDSCC2) and HPV-negative (OCT1) HNSCC cell lines. These exosomes were characterized for their potential to modulate macrophage polarization. Uptake of PKH-26 labeled exosomes by macrophages was monitored via confocal microscopy. Changes in macrophage polarization were assessed using quantitative real-time PCR and immunoblotting. Exosomal transcripts and proteome cargo was examined for polarization associated mediators.
RESULTS: HPV-negative exosomes showed higher uptake by THP1 resting macrophages (M0). Exosomes from HPV-positive cells induced a mixed macrophage phenotype (M1 and M2), whereas HPV-negative exosomes favored M1 polarization. Immunoblotting analysis revealed that this polarization was driven by the activation of transcription factors STAT1, NF-κB, and AP1. Transcriptomic analysis of HNSCC exosomes revealed reads for AP1 (c-Jun, c-Fos, FosB, Fra1, Fra2) and NF-κB (p50/105, p52/100, RelA, RelB, c-Rel), along with their known upstream mediators MEK1--7, JNK1-3, JAK1-3, TYK2, IKKα, and IKKβ. Splice variants of macrophage polarization markers, including iNOS and TGFβ, were also identified, though none of the exosomal proteome component corresponded to these factors.
CONCLUSION: HPV-negative exosomes are efficiently internalized by macrophages, promoting M1 polarization likely via modulation of STAT1, NF-κB, and AP1 signaling. These findings provide novel insights into role of tumor exosomes in modulation of macrophage-mediated TME dynamics in HNSCC.

Keywords:  Exosomes; Head and neck squamous cell carcinoma (HNSCC); Macrophage polarization; Signaling pathways; Tumor microenvironment (TME)

DOI:  https://doi.org/10.1016/j.cyto.2024.156831
Clin Transl Oncol. 2024 Dec 20.

Biogenesis and functional implications of extracellular vesicles in cancer metastasis.

Sneha Sekar, Sandhya Srikanth, Anirban Goutam Mukherjee, Abilash Valsala Gopalakrishnan, Uddesh Ramesh Wanjari, Balachandar Vellingiri, Kaviyarasi Renu, Harishkumar Madhyastha.

  Extracellular vesicles (EVs) play a crucial role in the complex process of cancer metastasis by facilitating cellular communication and influencing the microenvironment to promote the spread and establishment of cancer cells in distant locations. This paper explores the process of EV biogenesis, explaining their various sources that range from endosomal compartments to plasma membrane shedding. It also discusses the complex mechanisms that control the sorting of cargo within EVs, determining their chemical makeup. We investigate the several functions of EVs in promoting the spread of cancer to other parts of the body. These functions include influencing the immune system, creating environments that support the formation of metastases before they occur, and aiding in the transformation of cells from an epithelial to a mesenchymal state. Moreover, we explore the practical consequences of EV cargo, such as nucleic acids, proteins, and lipids, in influencing the spread of cancer cells, from the beginning of invasion to the creation of secondary tumor sites. Examining recent progress in the field of EV-based diagnostics and treatments, we explore the potential of EVs as highly promising biomarkers for predicting the course of cancer and as targets for therapeutic intervention. This review aims to provide a complete understanding of the biology of EVs in the context of cancer metastasis. By unravelling the nuances of EV biology, it seeks to pave the way for new tactics in cancer detection, treatment, and management.

Keywords:  Biogenesis; Biomarkers; Extracellular vesicles; Metastasis; Tumour microenvironment

DOI:  https://doi.org/10.1007/s12094-024-03815-8
Cell Death Dis. 2024 Dec 18. 15(12): 913

Exosomal miR-320d promotes angiogenesis and colorectal cancer metastasis via targeting GNAI1 to affect the JAK2/STAT3 signaling pathway.

Yawen Wu, Jie Zhang, Guanghao Li, Li Wang, Yajing Zhao, Baibing Zheng, Fanfeng Lin, Li Xie.

Colorectal cancer is a common malignant tumor, whose growth and metastasis are influenced by numerous factors. MicroRNAs have garnered increasing attention in recent years due to their involvement in tumor development. Exosomes are involved in intercellular signaling and influence tumor development by promoting tumor cell proliferation and metastasis through activation of angiogenesis and other mechanisms. This study aimed to investigate how the exosomes containing miR-320d from colorectal cancer (CRC) cells promote colorectal cancer metastasis by regulating angiogenesis. CRC-derived exosomes containing miR-320d can be transferred to vascular endothelial cells, facilitating their proliferation, invasion, migration, and angiogenesis. By targeting GNAI1, miR-320d in these exosomes reduces GNAI1 levels in endothelial cells, causing more JAK2/STAT3 activation and VEGFA production. This ultimately enhances the migration and angiogenic capacity of vascular endothelial cells. Moreover, CRC patients with high levels of miR-320d in their blood respond better to treatment with bevacizumab. In vivo experiments further proved the role of miR-320d from CRC exosomes in increasing tumor size, blood vessel formation, and the spread of cancer to the liver. In this study, we have demonstrated that exosomal miR-320d promotes cancer cell metastasis and enhances angiogenesis by downregulating GNAI1 expression and enhancing JAK2/STAT3.

DOI: https://doi.org/10.1038/s41419-024-07297-y
Cancers (Basel). 2024 Nov 25. pii: 3948. [Epub ahead of print]16(23):

Potential Use of Exosomal Non-Coding MicroRNAs in Leukemia Therapy: A Systematic Review.

Paulina Gil-Kulik, Natalia Kluz, Dominika Przywara, Alicja Petniak, Małgorzata Wasilewska, Natalia Frączek-Chudzik, Marek Cieśla.

  Leukemia is a heterogeneous group of hematological malignancies. Despite the enormous progress that has been made in the field of hemato-oncology in recent years, there are still many problems related to, among others, disease recurrence and drug resistance, which is why the search for ideal biomarkers with high clinical utility continues. Research shows that exosomes play a critical role in the biology of leukemia and are associated with the drug resistance, metastasis, and immune status of leukemias. Exosomes with their cargo of non-coding RNAs act as a kind of intermediary in intercellular communication and, at the same time, have the ability to manipulate the cell microenvironment and influence the reaction, proliferative, angiogenic, and migratory properties of cells. Exosomal ncRNAs (in particular, circRNAs and microRNAs) appear to be promising cell-free biomarkers for diagnostic, prognostic, and treatment monitoring of leukemias. This review examines the expression of exosomal ncRNAs in leukemias and their potential regulatory role in leukemia therapy but also in conditions such as disease relapse, drug resistance, metastasis, and immune status. Given the key role of ncRNAs in regulating gene networks and intracellular pathways through their ability to interact with DNA, transcripts, and proteins and identifying their specific target genes, defining potential functions and therapeutic strategies will provide valuable information.

Keywords:  exosomes; leukemia; microRNA; ncRNA; therapy

DOI:  https://doi.org/10.3390/cancers16233948
Int J Mol Sci. 2024 Nov 21. pii: 12524. [Epub ahead of print]25(23):

Glioma-Derived Exosomes and Their Application as Drug Nanoparticles.

Serena Mastantuono, Ivana Manini, Carla Di Loreto, Antonio Paolo Beltrami, Marco Vindigni, Daniela Cesselli.

  Glioblastoma Multiforme (GBM) is the most aggressive primary tumor of the Central Nervous System (CNS) with a low survival rate. The malignancy of GBM is sustained by a bidirectional crosstalk between tumor cells and the Tumor Microenvironment (TME). This mechanism of intercellular communication is mediated, at least in part, by the release of exosomes. Glioma-Derived Exosomes (GDEs) work, indeed, as potent signaling particles promoting the progression of brain tumors by inducing tumor proliferation, invasion, migration, angiogenesis and resistance to chemotherapy or radiation. Given their nanoscale size, exosomes can cross the blood-brain barrier (BBB), thus becoming not only a promising biomarker to predict diagnosis and prognosis but also a therapeutic target to treat GBM. In this review, we describe the structural and functional characteristics of exosomes and their involvement in GBM development, diagnosis, prognosis and treatment. In addition, we discuss how exosomes can be modified to be used as a therapeutic target/drug delivery system for clinical applications.

Keywords:  exosomes; glioblastoma multiforme; glioma-derived exosomes; tumor microenvironment

DOI:  https://doi.org/10.3390/ijms252312524