bims-exocan 2024-06-23 papers

bims-exocan

Biomed News

on Exosomes roles in cancer

Issue of 2024‒06‒23
six papers selected by
Muhammad Rizwan, COMSATS University

Exosomes derived from colorectal cancer cells take part in activation of stromal fibroblasts through regulating PHLPP isoforms.
CAR-T cell-derived exosomes: a new perspective for cancer therapy.
In Vitro and In Vivo Analyses Reveal Tumor-Derived Exosome miR-558 Promotes Angiogenesis in Tongue Squamous Cell Carcinoma by Targeting Heparinase.
Exosomes as drug delivery systems in glioma immunotherapy.
Molecular insights to therapeutic in cancer: role of exosomes in tumor microenvironment, metastatic progression and drug resistance.
Salivary exosomal microRNA profile as biomonitoring tool for diagnosis and prognosis of patients with head and neck squamous cell carcinoma: a systematic review.

EXCLI J. 2024 ;23 634-654

Exosomes derived from colorectal cancer cells take part in activation of stromal fibroblasts through regulating PHLPP isoforms.

Fatemeh Khaloozadeh, Ehsan Razmara, Fatemeh Asgharpour-Babayian, Alireza Fallah, Reihaneh Ramezani, Fatemeh Rouhollah, Sadegh Babashah.

  Given that tumor cells primarily instigate systemic changes through exosome secretion, our study delved into the role of colorectal cancer (CRC)-secreted exosomal miR-224 in stromal reprogramming and its impact on endothelial cell angiogenesis. Furthermore, we assessed the potential clinical significance of a specific signature of circulating serum-derived miRNAs, serving as a non-invasive biomarker for CRC diagnosis. Circulating serum-derived miR-103a-3p, miR-135b-5p, miR-182-5p, and miR-224-5p were significantly up-regulated, while miR-215-5p, and miR-455-5p showed a significant down-regulation in CRC patients than in healthy individuals. Our findings indicated that the expressions of CAF-specific markers (α-SMA and FAP) and CAF-derived cytokines (IL-6, and SDF-1) were induced in fibroblasts stimulated with SW480 CRC exosomes, partly due to Akt activation. As a plausible mechanism, exosomal transfer of miR-224 from SW40 CRC cells may activate stromal fibroblasts, which in turn, may promote endothelial cell sprouting. The study identified PHLPP1 and PHLPP2 as direct targets of miR-224 and demonstrated that CRC-secreted exosomal miR-224 activates Akt signaling by regulating PHLPP1/2 in activated fibroblasts, thereby affecting the stromal cell proliferation and migration. This study established a panel of six-circulating serum-derived miRNAs as a non-invasive biomarker for CRC diagnosis. Also, we proposed a supporting model in which CRC-secreted exosomal miR-224 takes part in the stromal reprogramming to CAFs partly through regulating Akt signaling. This may affect the malignant biological behavior of activated stromal cells and thereby elicit a vascular response within the microenvironment of CRC cells. See also the graphical abstract(Fig. 1).

Keywords:  Akt signaling; PHLPPs; cancer associated fibroblasts; colorectal cancer; exosomes; miR-224

DOI:  https://doi.org/10.17179/excli2024-6926
Stem Cell Res Ther. 2024 Jun 18. 15(1): 174

CAR-T cell-derived exosomes: a new perspective for cancer therapy.

Farnaz Sani, Shabnam Shojaei, Seyed Amirhossein Tabatabaei, Mohammadhossein Khorraminejad-Shirazi, Mona Latifi, Mahsa Sani, Negar Azarpira.

  Chimeric antigen receptor (CAR)-T cell adoptive immunotherapy is a promising cancer treatment that uses genetically engineered T cells to attack tumors. However, this therapy can have some adverse effects. CAR-T cell-derived exosomes are a potential alternative to CAR-T cells that may overcome some limitations. Exosomes are small vesicles released by cells and can carry a variety of molecules, including proteins, RNA, and DNA. They play an important role in intercellular communication and can be used to deliver therapeutic agents to cancer cells. The application of CAR-T cell-derived exosomes could make CAR-T cell therapy more clinically controllable and effective. Exosomes are cell-free, which means that they are less likely to cause adverse reactions than CAR-T cells. The combination of CAR-T cells and exosomes may be a more effective way to treat cancer than either therapy alone. Exosomes can deliver therapeutic agents to cancer cells where CAR-T cells cannot reach. The appropriate application of both cellular and exosomal platforms could make CAR-T cell therapy a more practicable treatment for cancer. This combination therapy could offer a safe and effective way to treat a variety of cancers.

Keywords:  CAR-T cell; Cancer; Cell therapy; Exosome; Solid tumor

DOI:  https://doi.org/10.1186/s13287-024-03783-4
Technol Cancer Res Treat. 2024 Jan-Dec;23:23 15330338241261615

In Vitro and In Vivo Analyses Reveal Tumor-Derived Exosome miR-558 Promotes Angiogenesis in Tongue Squamous Cell Carcinoma by Targeting Heparinase.

Bixiao Ding, Qingwen Chen, Zhen Wu, Xiaoguang Li, Yuancheng Ding, Qiong Wu, Liang Han, Hao Wu.

  This study aimed to investigate the role of miR-558 in tumor angiogenesis by targeting heparinase (HPSE) in tongue squamous cell carcinoma (TSCC)-derived exosomes. In the present study, the role of exosome miR-558 in angiogenesis in vitro and in vivo was investigated by cell proliferation, migration, tube formation, subcutaneous tumor formation in mice, and in vivo Matrigel plug assay. The target genes of miR-558 were detected by means of dual luciferase assay. It was found that TSCC cells secrete miR-558 into the extracellular environment, with exosome as the carrier. Human umbilical vein endothelial cells (HUVEC) ingested exosomes, which not only increased the expression level of miR-558, but also enhanced their proliferation, migration, and tube formation functions. In vivo Matrigel plug assay demonstrated that TSCC cell-derived exosome miR-558 promoted neovascularization in vivo. Compared with negative control cells, TSCC cells overexpressing miR-558 formed subcutaneous tumors in nude mice, with larger volume, heavier mass, and more vascularization. Dual luciferase assay confirmed that HPSE was the direct target gene regulated by miR-558. HPSE promoted the proliferation, migration, and tube formation of HUVECs, and the knockout of HPSE could downregulate the pro-angiogenic effect of miR-558. In summary, miR-558 in TSCC exosomes promotes the proliferation, migration, and tube formation of HUVECs by targeting HPSE, and enhancing tumor angiogenesis.

Keywords:  HPSE; angiogenesis; exosomes; miR-558; tongue squamous cell carcinoma

DOI:  https://doi.org/10.1177/15330338241261615
J Nanobiotechnology. 2024 Jun 18. 22(1): 340

Exosomes as drug delivery systems in glioma immunotherapy.

Xinqing Hao, Shiming Wang, Liang Wang, Jiaqi Li, Ying Li, Jing Liu.

  Recently, the significant benefits of cancer immunotherapy for most cancers have been demonstrated in clinical and preclinical studies. However, the efficacy of these immunotherapies for gliomas is limited, owing to restricted drug delivery and insufficient immune activation. As drug carriers, exosomes offer the advantages of low toxicity, good biocompatibility, and intrinsic cell targeting, which could enhance glioma immunotherapy efficacy. However, a review of exosome-based drug delivery systems for glioma immunotherapy has not been presented. This review introduces the current problems in glioma immunotherapy and the role of exosomes in addressing these issues. Meanwhile, preparation and application strategies of exosome-based drug delivery systems for glioma immunotherapy are discussed, especially for enhancing immunogenicity and reversing the immunosuppressive tumor microenvironment. Finally, we briefly describe the challenges of exosome-based drug delivery systems in clinical translation. We anticipate that this review will guide the use of exosomes as drug carriers for glioma immunotherapy.

Keywords:  Drug delivery systems; Exosomes; Glioma; Immunotherapy

DOI:  https://doi.org/10.1186/s12951-024-02611-4
Drug Discov Today. 2024 Jun 18. pii: S1359-6446(24)00186-7. [Epub ahead of print] 104061

Molecular insights to therapeutic in cancer: role of exosomes in tumor microenvironment, metastatic progression and drug resistance.

Shikshya S Panda, Rajeev K Sahoo, Sambit K Patra, Stuti Biswal, Bijesh K Biswal.

  Exosomes play a pivotal part in cancer progression and metastasis by transferring various biomolecules. Recent research highlights their involvement in tumor microenvironment remodeling, mediating metastasis, tumor heterogeneity and drug resistance. The unique cargo carried by exosomes garners the interest of researchers owing to its potential as a stage-specific biomarker for early cancer detection and its role in monitoring personalized treatment. However, unanswered questions hinder a comprehensive understanding of exosomes and their cargo in this context. This review discusses recent advancements and proposes novel ideas for exploring exosomes in cancer progression, aiming to deepen our understanding and improve treatment approaches.

Keywords:  Cancer; drug resistance; exosome; metastasis; tumor heterogeneity; tumor microenvironment

DOI:  https://doi.org/10.1016/j.drudis.2024.104061
Arch Oral Biol. 2024 May 27. pii: S0003-9969(24)00133-X. [Epub ahead of print]165 106012

Salivary exosomal microRNA profile as biomonitoring tool for diagnosis and prognosis of patients with head and neck squamous cell carcinoma: a systematic review.

Lorenzo Sanesi, Giorgio Mori, Giuseppe Troiano, Andrea Ballini, Felice Valzano, Mario Dioguardi, Lorenzo Lo Muzio, Marco Magalhaes, Vito Carlo Alberto Caponio.

  OBJECTIVE: Exosomes are extracellular vesicles found in saliva and other body fluids. These vesicles range in size from 30 to 150 nm and play a crucial role in intercellular communication, transporting different biomolecules, actively targeting cells. These vesicles regulate both physiological and pathological processes within recipient cells. MicroRNAs (miRs) are transported within exosomes and are delivered to target cells where they influence signaling pathways, taking on a crucial regulatory role in oncogenesis; for example, they are implicated in progression and infiltration of various cancers, such as head and neck squamous cell carcinoma (HNSCC).MATERIAL AND METHODS: A systematic literature search based on specific keywords, according to the PRISMA guidelines, was carried out on PubMed, Web of Science, Scopus, and Google Scholar. Only original articles were selected during this review. The risk of bias was assessed by QUADAS-2.
RESULTS: At the end of the selection process 9 articles were included. In these studies, 41 miRs showed differential expression between healthy subjects and patient with HNSCC. The techniques varied among studies for the extraction and analysis of exosomal miRs. We presented also salivary exosomal miRs pathways, to give insights about pathogenetic mechanisms.
CONCLUSIONS: Exosomal microRNA are promising biomarkers for HNSCC detection. MiR-10b-5p, miR-486-5p, miR-24-3p, miR-412-3p, and miR-512-3p are the most promising markers applicable to diagnostics, while miR-1307-5p and miR-519c-3p resulted overexpressed and correlated to worse survival outcomes.

Keywords:  Biomarkers; Diagnosis; Head and Neck Neoplasms; MicroRNAs; Mouth Neoplasms; Prognosis

DOI:  https://doi.org/10.1016/j.archoralbio.2024.106012