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The impact of hypoxia on extracellular vesicle secretome profile of cancer

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Abstract

Extracellular vesicles (EVs) are emerging as key mediators of cell-to-cell communications and signal transporters between tumor and stroma, and hypoxia is a critical characteristic of tumor microenvironment (TME) in solid cancers. Hypoxia stimulates tumor cells to generate and secrete more EVs, and the EVs shed from cancer transfer biological information to boost hypoxia and hypoxia inducible factor (HIF) functionality. Hypoxia alters EV secretome profile to carry pro-tumorigenic factors for promoting numerous tumor-related processes including increased cancer cell proliferation and survival, immune escape, aberrant angiogenesis, and invasion and metastasis. Exosomal hypoxia inducible factor (HIF)-1α is an essential driver of epithelial-mesenchymal transition (EMT) and stemness profile in cancer. Hypoxic cancer-derived EVs are also contributed to therapy resistance. In fact, EVs are messengers of hypoxic tolerance in cancer, which enable adaptation of tumor cells to changes occurring within TME for their further resistance and metastasis. Tracing EVs shed from hypoxic tumor cells into plasma provide important information about the genomic signature of cancer. In this review, we aimed to discuss about key tumorigenic events promoted by inter-connections between hypoxia and EVs, mainly exosomes, secreted into tumor area focusing on key hallmarks of cancer.

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Acknowledgements

This work received ethical approval from Kurdistan University of Medical Sciences (Ethical code: IR.MUK.REC.1401.428).

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  1. Department of Anatomy, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran

    Keywan Mortezaee

  2. Department of Anatomy, School of Medicine, Infectious Diseases Research Center, Gonabad University of Medical Sciences, Gonabad, Iran

    Jamal Majidpoor

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Conceptualization, KM; article collection and scanning, KM; writing original. Draft, review and editing, KM and JM. Authors have read and agreed to publish the manuscript.

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Correspondence to Keywan Mortezaee.

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Mortezaee, K., Majidpoor, J. The impact of hypoxia on extracellular vesicle secretome profile of cancer. Med Oncol 40, 128 (2023). https://doi.org/10.1007/s12032-023-01995-x

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