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Exosomes and cancer: from molecular mechanisms to clinical applications

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Abstract

Exosomes are extracellular nanovesicles secreted from almost all types of normal and cancer cells. Collective evidence suggests that exosomes participate in cell–cell communication via transmitting their cargo, including nucleic acids, proteins, and metabolites to recipient cells. Tumor-derived exosomes (TEXs) play prominent roles in the regulation of molecular pathways in malignancies. Internalization of exosomes by tumor cells affects cellular pathways and several cancer hallmarks, including reprogramming of stromal cells, modulating immune responses, reconstructing extracellular matrix architecture, or even endowing tumor cells with drug features resistance. The unique biogenesis pathways of exosomes, their composition, low immunogenicity, and nontoxicity, together with their ability to target tumor cells, bring them up as an attractive vesicles for cancer therapy. Thus, understanding the molecular mechanisms of exosomes' participation in tumorigenesis will be critical for the next generation of cancer therapeutics. This review aims to summarize the exosomes' roles in different mechanisms underlying cancer progression for the rational design of tailored strategies against this illness. The present study also highlights the new findings on using these smart vesicles as therapeutic targets and potential biomarkers. Recent advances in exosome biology will open up new, more effective, less invasive, and more individualized clinical applications for treating cancer patients.

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Abbreviations

ABCs:

ATP-binding cassette transporters

AD:

Alzheimer's disease

Aβ:

β-Amyloid

bFGF:

Basic fibroblast growth factor

CNS:

Central nervous system

CSF:

Cerebrospinal fluid

DCs:

Dendritic cells

EMT:

Epithelial to mesenchymal transition

ERK1/2:

Extracellular signal‑regulated protein kinase

EVs:

Extracellular vesicles

FAK:

Focal adhesion kinase

HSP:

Heat shock protein

IFN:

Interferon

IL:

Interleukin

MAPK:

Mitogen-activated protein kinase

MHC:

Major histocompatibility complex

MMP:

Matrix metalloproteinase

MSCs:

Mesenchymal stem cells

MVBs:

Multivesicular bodies

NF-κB:

Nuclear factor κB

NOS:

Nitric oxide synthase

NSCLC:

Non-small cell lung cancer

PD-1:

Programmed death 1

PDGF:

Platelet-derived growth factor

P-gp:

P-glycoprotein

PI3K/Akt:

Phosphoinositide 3-kinase/protein kinase B

TERT:

Telomerase reverse transcriptase

TEXs:

Tumor-derived exosomes

TGF-β:

Transforming growth factor β

TME:

Tumor microenvironment

VEGF:

Vascular endothelial growth factor

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Acknowledgment

The authors would also like to express their most sincere words of appreciation to Dr. Elham Jamshidi for her valuable contribution.

Funding

This study is related to project NO 1398/4083 From the Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran. We also appreciate the "Student Research Committee" and "Research & Technology Chancellor" at Shahid Beheshti University of Medical Sciences for their financial support of this study.

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Author notes

  1. Ameneh Jafari and Amirhesam Babajani are share the first authorship.

Authors and Affiliations

  1. Student Research Committee, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Ameneh Jafari

  2. Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Ameneh Jafari, Nayebali Ahmadi & Mostafa Rezaei-Tavirani

  3. Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Amirhesam Babajani

  4. Cellular and Molecular Biology Research Center, Larestan University of Medical Sciences, Larestan, Iran

    Meghdad Abdollahpour-Alitappeh

  5. Proteomics Research Center, Department of Medical Lab Technology, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Nayebali Ahmadi

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  4. Nayebali Ahmadi
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  5. Mostafa Rezaei-Tavirani
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Contributions

Conceptualization: AJ, AB, NA, MRT and MA; investigation: AJ, AB, MA, NA; writing—original draft preparation: AJ, AB; writing—review and editing: AJ, AB, and MA; supervision: MRT. All authors read and agreed to the published version of the manuscript.

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Correspondence to Mostafa Rezaei-Tavirani.

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Jafari, A., Babajani, A., Abdollahpour-Alitappeh, M. et al. Exosomes and cancer: from molecular mechanisms to clinical applications. Med Oncol 38, 45 (2021). https://doi.org/10.1007/s12032-021-01491-0

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