bims-exocan 2024-02-25 papers

Issue of 2024–02–25
six papers selected by
Muhammad Rizwan, COMSATS University

ACS Appl Bio Mater. 2024 Feb 23.

Exosomes: A Cutting-Edge Theranostics Tool for Oral Cancer.

Ketki Kalele, Sidhanti Nyahatkar, Divya Mirgh, Raman Muthuswamy, Manab Deb Adhikari, Krishnan Anand.

Exosomes are a subpopulation of extracellular vesicles (EVs) secreted by cells. In cancer, they are key cellular messengers during cancer development and progression. Tumor-derived exosomes (TEXs) promote cancer progression. In oral cancer, the major complication is oral squamous cell carcinoma (OSCC). Exosomes show strong participation in several OSCC-related activities such as uncontrolled cell growth, immune suppression, angiogenesis, metastasis, and drug and therapeutic resistance. It is also a potential biomarker source for oral cancer. Some therapeutic exosome sources such as stem cells, plants (it is more effective compared to others), and engineered exosomes reduce oral cancer development. This therapeutic approach is effective because of its specificity, biocompatibility, and cell-free therapy (it reduced side effects in cancer treatment). This article highlights exosome-based theranostics signatures in oral cancer, clinical trials, challenges of exosome-based oral cancer research, and future improvements. In the future, exosomes may become an effective and affordable solution for oral cancer.

Keywords: biomarker; exosomes; metastasis; oral squamous cell carcinoma; therapeutics

DOI: https://doi.org/10.1021/acsabm.3c01243

Cancers (Basel). 2024 Feb 18. pii: 823. [Epub ahead of print]16(4):

Exosomes in Glioma: Unraveling Their Roles in Progression, Diagnosis, and Therapy.

Song Yang, Yumeng Sun, Wei Liu, Yi Zhang, Guozhu Sun, Bai Xiang, Jiankai Yang.

Gliomas, the most prevalent primary malignant brain tumors, present a challenging prognosis even after undergoing surgery, radiation, and chemotherapy. Exosomes, nano-sized extracellular vesicles secreted by various cells, play a pivotal role in glioma progression and contribute to resistance against chemotherapy and radiotherapy by facilitating the transportation of biological molecules and promoting intercellular communication within the tumor microenvironment. Moreover, exosomes exhibit the remarkable ability to traverse the blood-brain barrier, positioning them as potent carriers for therapeutic delivery. These attributes hold promise for enhancing glioma diagnosis, prognosis, and treatment. Recent years have witnessed significant advancements in exosome research within the realm of tumors. In this article, we primarily focus on elucidating the role of exosomes in glioma development, highlighting the latest breakthroughs in therapeutic and diagnostic approaches, and outlining prospective directions for future research.

Keywords: diagnosis; drug delivery system; exosomes; gliomas; treatment

DOI: https://doi.org/10.3390/cancers16040823

J Biochem Mol Toxicol. 2024 Mar;38(3): e23666

Exosomal miR-93 derived from hepatocellular carcinoma cell promotes the sorafenib resistance of hepatocellular carcinoma through PTEN/PI3K/Akt pathway.

Yuanpeng Bao, Song Xu, Junjing Zhou, Chongyong Zhao, Saimin Dai, Yong Zhang, Min Rao.

Exosomal microRNAs (miRNAs) derived from cancer cell is an important regulatory molecule that mediates the formation of tumor drug resistance, but function and mechanisms of exosomal miRNA in sorafenib resistance of hepatocellular carcinoma (HCC) have not been studied. We detected the level and prognosis of miR-93 in HCC by using TCGA HCC database. For confirming the extracted exosome, transmission electron microscopy was used. Cy3-labeled miR-93 and quantitative reverse transcription-polymerase chain reaction were used to prove that exosomal miR-93 derived from HCC cell can be transferred to sensitive HCC cells. CCK8, EdU, and flow cytometer assay were used to confirm the function of exosomal miR-93 in sorafenib resistance of HCC. Bioinformatics software and luciferase reporter assay was used to confirm the direct targeting relationship between PTEN and miR-93. Western blot was used to validate downstream pathways. We found that miR-93 is overexpressed and a prognostic risk factor for the HCC patients. miR-93 was overexpressed in sorafenib resistant HCC cells compared with sensitive cells, and miR-93 contributed to sorafenib resistance of HCC cells through targeting PTEN. miR-93 was enriched in exosomes that secreted from sorafenib resistant cells, and these exosomal miR-93 promote the spread of sorafenib resistant through targeting PTEN to reactivate PI3K/AKT pathway. Therefore, miR-93 can act as a potential therapeutic target for advanced patients with acquired sorafenib resistance.

Keywords: HCC; PTEN; exosome; miR-93; sorafenib resistance

DOI: https://doi.org/10.1002/jbt.23666

Pharmacol Rep. 2024 Feb 22.

Diagnostic, prognostic, and therapeutic potential of exosomal microRNAs in renal cancer.

Xiaodong Yu, Zhongbo Du, Pingyu Zhu, Bo Liao.

Renal cell carcinoma (RCC) arises from the tubular epithelial cells of the nephron. It has the highest mortality rate among urological cancers. There are no effective therapeutic approaches and no non-invasive biomarkers for diagnosis and follow-up. Thus, suitable novel biomarkers and therapeutic targets are essential for improving RCC diagnosis/prognosis and treatment. Circulating exosomes such as exosomal microRNAs (Exo-miRs) provide non-invasive prognostic/diagnostic biomarkers and valuable therapeutic targets, as they can be easily isolated and quantified and show high sensitivity and specificity. Exosomes secreted by an RCC can exhibit alterations in the miRs' profile that may reflect the cellular origin and (patho)physiological state, as a ''signature'' or ''fingerprint'' of the donor cell. It has been shown that the transportation of renal-specific miRs in exosomes can be rapidly detected and measured, holding great potential as biomarkers in RCC. The present review highlights the studies reporting tumor microenvironment-derived Exo-miRs with therapeutic potential as well as circulating Exo-miRs as potential diagnostic/prognostic biomarkers in patients with RCC.

Keywords: Diagnosis; Exosome; MicroRNA; Prognosis; Renal cell carcinoma; Therapy

DOI: https://doi.org/10.1007/s43440-024-00568-7

Pathol Oncol Res. 2024 ;30 1611549

Extracellular vesicles as modulators of glioblastoma progression and tumor microenvironment.

Jie Dai, Yong Jiang, Haoyue Hu, Shuang Zhang, Yue Chen.

Glioblastoma is the most aggressive brain tumor with extremely poor prognosis in adults. Routine treatments include surgery, chemotherapy, and radiotherapy; however, these may lead to rapid relapse and development of therapy-resistant tumor. Glioblastoma cells are known to communicate with macrophages, microglia, endothelial cells, astrocytes, and immune cells in the tumor microenvironment (TME) to promote tumor preservation. It was recently demonstrated that Glioblastoma-derived extracellular vesicles (EVs) participate in bidirectional intercellular communication in the TME. Apart from promoting glioblastoma cell proliferation, migration, and angiogenesis, EVs and their cargos (primarily proteins and miRNAs) can act as biomarkers for tumor diagnosis and prognosis. Furthermore, they can be used as therapeutic tools. In this review, the mechanisms of Glioblastoma-EVs biogenesis and intercellular communication with TME have been summarized. Moreover, there is discussion surrounding EVs as novel diagnostic structures and therapeutic tools for glioblastoma. Finally, unclear questions that require future investigation have been reviewed.

Keywords: exosomes; extracellular vesicles; glioblastoma; microvesicles; tumor microenvironment

DOI: https://doi.org/10.3389/pore.2024.1611549

Exp Cell Res. 2024 Feb 19. pii: S0014-4827(24)00053-3. [Epub ahead of print] 113963

Tumor-derived exosomal hyaluronidase 1 induced M2 macrophage polarization and promoted esophageal cancer progression.

Jinyan Yuan, Bin Hou, Kai Guo, Jianfei Zhu, Haimin Xiao.

The communication between tumor-derived exosomes and macrophages plays an important role in facilitating the progression of tumors. However, the regulatory mechanisms by which exosomes regulate tumor progression in esophageal squamous cell carcinoma (ESCC) have not been fully elucidated. We constructed a coculture system containing an ESCC cell line and macrophages using a Transwell chamber. We isolated exosomes from the conditioned medium of cancer cells, and characterized them with transmission electron microscopy and western blotting and used then to treat macrophages. We used co-immunoprecipitation to evaluate the interaction between hyaluronidase 1 (HYAL1) and Aurora B kinase (AURKB). We evaluated HYAL1 and AURKB expression in tissues and cells with quantitative reverse-transcription polymerase chain reaction (RT-qPCR) and western blotting. We used RT-qPCR, enzyme-linked immunosorbent assay (ELISA) and flow cytometry to detect macrophage polarization. We assessed cell viability, invasion and migration with the cell counting kit-8 (CCK-8), Transwell and wound healing assays. HYAL1 was highly expressed in ESCC tissues and cells and cancer cell-derived exosomes, and exosomes can be delivered to macrophages through the cancer cell-derived exosomes. The exosomes extracted from HYAL1-overexpressed ESCC cells suppressed M1 macrophage polarization and induced M2 macrophage polarization, thereby promoting ESCC cell viability, invasion and migration. HYAL1 silencing in ESCC cells produced the opposite effects on macrophage polarization and cancer cell functions. We found that HYAL1 interacted with AURKB and further activated the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway in macrophages. In conclusion, ESCC-derived exosomes containing HYAL1 facilitate M2 macrophage polarization by targeting AURKB to active the PI3K/AKT signaling pathway, which in turn promotes ESCC progression.

Keywords: Esophageal cancer; Exosomes; HYAL1; Macrophages polarization

DOI: https://doi.org/10.1016/j.yexcr.2024.113963