bims-exocan 2025-04-13 papers

Issue of 2025–04–13
four papers selected by
Muhammad Rizwan, COMSATS University

Cell Biochem Biophys. 2025 Apr 11.

Impaired Cellular Cholesterol Homeostasis Decreases Tumor-Derived Exosome Load And Modulates Malignant Transformation in Cancer Cells.

Syed Sultan Beevi, Aishwarya Sudam Bhale, Vinod Kumar Verma, Radhika Chowdary Darapuneni.

Tumor-derived exosomes (TDEs) play a crucial role in horizontally transferring oncogenic information from tumors to other sites. Cellular cholesterol homeostasis has emerged as a significant factor influencing exosomal biogenesis and cellular release. In this study, we employed U18666A to induce cholesterol accumulation within the late endosomes of MDA-MB231 cells. We assessed the capacity of exosomes derived from U18666A-treated and untreated cells to initiate malignant transformation in HEK293 cells. Exosomes were isolated and characterized from both untreated and U18666A-treated MDA-MB231 cells, and HEK293 cells. The impact of exosomes derived from untreated MDA-MB231 cells (referred to as UCE) and U18666A-treated MDA-MB231 cells (referred to as UTCE) to induce transformation on HEK293 cells was investigated. Exosomes derived from MDA-MB231 cells induced proliferation, migration, malignant transformation, and epithelial-mesenchymal transition (EMT) process in HEK293 cells. Treatment with U18666A resulted in cholesterol accumulation within late endosomes, consequently markedly reversing the EMT process in MDA-MB231 cells. This treatment diminished the content of Tumor-derived exosomes released by the cancer cells, rendering them less oncogenic. This reduction in oncogenic potential was evident as they lost the ability to induce malignant transformation in recipient HEK293 cells. Modulating cholesterol homeostasis and disrupting the supply of cholesterol to aggressive cancer cells emerges as an appealing strategy to restrain the release of Tumor-derived exosomes and subsequently mitigate their contributory role in driving cancer progression and metastasis.

Keywords: Cryo-SEM; EMT process; Filipin staining; Foci formation; Nano-tracking analysis; Scratch assay

DOI: https://doi.org/10.1007/s12013-025-01744-z

Med Oncol. 2025 Apr 10. 42(5): 159

Secretory exosomes from modified immune cells against cancer.

Asrin Mafakheri, Fardin Fathi, Jamal Majidpoor, Hasan Moayeri, Keywan Mortezaee.

Extracellular vesicles (EVs) play significant roles in cancer progression through mediating inter/intra cellular communications within tumor microenvironment (TME). EVs are used as non-invasive diagnostic tools, drug delivery systems, and cancer vaccines, considering the anti-tumor potential, safety, biocompatibility and physiochemical stability of endogenous EVs. Modification of immune cells, either genetically or epigenetically, is a growing field of cancer research with the goal of enhancing efficacy of immunotherapy. This review focuses on the possibility of manipulating immune cells including dendritic cells (DCs), natural killer (NK) cells and T cells to secrete EVs that exert immune function either by activating immune responses or altering immune cell behavior to enhance anti-tumor efficacy, and discusses potential obstacles and recommendations for improved functionality of this therapeutic method.

Keywords: Cancer vaccination; Dendritic cell-derived exosome (DEX); Exosome; Extracellular vesicle (EV); Natural killer (NK)

DOI: https://doi.org/10.1007/s12032-025-02706-4

Biochem Biophys Res Commun. 2025 Apr 01. pii: S0006-291X(25)00449-8. [Epub ahead of print]761 151735

Exosomal 4EBP1 promotes head and neck cancer progression via regulating mitochondrial fission.

Iyyannar Madhu, Anbarasu Kannan.

Head and neck cancer (HNC) is the sixth most common cancer around the globe with raised incidence and mortality. Despite the advancement in diagnostic and therapeutic approaches the burden of HNC has not reduced. Therefore, investigation on key molecular mechanisms that contributes to the progression of HNC is required to identify promising therapeutic targets. Exosomes are nanosized vesicles and recently emerged as a carrier of tumorigenic proteins essential for cancer progression. However, the role of exosomal proteins in HNC progression remains largely unclear. Eukaryotic Initiation Factor 4E-Binding protein 1 (4EBP1) regulates the protein synthesis and plays a crucial role in the progression of different forms of cancer. Our current study revealed that 4EBP1 is carried in human serum exosomes and upregulated in HNC serum exosomes than healthy controls (HC) and we observed that coculturing the 4EBP1 upregulated HNC serum exosomes (HNC Exo) promoted the growth and migration of HEp-2 cells. Further, we examined the underlying mechanism by knockdown of 4EBP1 in HEp-2 cells (4EBP1 KD). Our results showed that knockdown of 4EBP1 have suppressed the migration and progression of cancer cells. Mechanistically, knockdown of 4EBP1 downregulated mitochondrial fission modulators DRP1 and FIS1 and attenuated the migration of HNC cancer cells by suppressing TGFβ and upregulating PTEN. Together our findings suggest that 4EBP1 is upregulated in circulating exosomes and promotes HNC progression via modulating mitochondrial fission and could be a potential therapeutic target for HNC.

Keywords: 4EBP1; DRP1; Exosomes; FIS1; Head and neck cancer; PTEN; TGFβ

DOI: https://doi.org/10.1016/j.bbrc.2025.151735

Int Immunopharmacol. 2025 Apr 07. pii: S1567-5769(25)00509-0. [Epub ahead of print]155 114519

Exosomal PD-L1 in non-small cell lung Cancer: Implications for immune evasion and resistance to immunotherapy.

Mojtaba Tarin, Mahsa Akbari Oryani, Hossein Javid, Mehdi Karimi-Shahri.

Exosomes, characterized by their bilayer lipid structure, are crucial in mediating intercellular signaling and contributing to various physiological processes. Tumor cells produce distinct exosomes facilitating cancer progression, angiogenesis, and metastasis by conveying signaling molecules. A notable feature of these tumor-derived exosomes is the presence of programmed death-ligand 1 (PD-L1) on their surface. The PD-L1/programmed cell death receptor-1 (PD-1) signaling axis serves as a critical immune checkpoint, enabling tumors to evade immune detection and antitumor activity. The advancement of immunotherapy targeting the PD-1/PD-L1 pathway has significantly impacted the treatment landscape for non-small cell lung cancer (NSCLC). Despite its promise, evidence indicates that many patients experience limited responses or develop resistance to PD-1/PD-L1 inhibitors. Recent studies suggest that exosomal PD-L1 contributes to this resistance by modulating immune responses and tumor adaptability. This study reviews the PD-1/PD-L1 pathway's characteristics, current clinical findings on PD-L1 inhibitors in NSCLC, and exosome-specific attributes, with a particular focus on exosomal PD-L1. Furthermore, it examines the growing body of research investigating the role of exosomal PD-L1 in cancer progression and response to immunotherapy, underscoring its potential as a target for overcoming resistance in NSCLC treatment.

Keywords: Exosomes; Immunotherapy; Non-small cell lung cancer; PD-1; PD-L1; Programmed death-ligand 1

DOI: https://doi.org/10.1016/j.intimp.2025.114519