Mechanism of Extracellular Vesicle Secretion Associated with TGF-β-Dependent Inflammatory Response in the Tumor Microenvironment

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Dec 11

PMID 36499660

Authors

Klaudia Bonowicz

Klaudia Mikolajczyk

Inaz Faisal

Murtaz Qamar

Kerstin Steinbrink

Konrad Kleszczynski

Alina Grzanka

Maciej Gagat

Affiliations

Soon will be listed here.

Abstract

Extracellular vesicles (EVs) serve as central mediators in communication between tumor and non-tumor cells. These interactions are largely dependent on the function of the endothelial barrier and the set of receptors present on its surface, as endothelial cells (ECs) are a plenteous source of EVs. The molecular basis for EV secretion and action in the tumor microenvironment (TME) has not been fully elucidated to date. Emerging evidence suggests a prominent role of inflammatory pathways in promoting tumor progression and metastasis. Although transforming growth factor β (TGF-β) is a cytokine with strong immunomodulatory and protective activity in benign and early-stage cancer cells, it plays a pro-tumorigenic role in advanced cancer cells, which is known as the "TGF-β paradox". Thus, the aim of this review is to describe the correlation between EV release, TGF-β-dependent inflammation, and dysregulation of downstream TGF-β signaling in the context of cancer development.

Citing Articles

Moxibustion Alleviates Inflammation via SIRT5-mediated Post-translational Modification and Macrophage Polarization.

Zuo C, Zhang C, Zhang H, Gou C, Lei H, Tian F Inflammation. 2025; .

PMID: 39899130 DOI: 10.1007/s10753-025-02239-y.

The role of platelet-rich plasma in biomedicine: A comprehensive overview.

Zhang Z, Liu P, Xue X, Zhang Z, Wang L, Jiang Y iScience. 2025; 28(2):111705.

PMID: 39898035 PMC: 11787504. DOI: 10.1016/j.isci.2024.111705.

Menopause mysteries: the exosome-inflammation connection.

Sultania A, Brahadeeswaran S, Kolasseri A, Jayanthi S, Tamizhselvi R J Ovarian Res. 2025; 18(1):12.

PMID: 39849635 PMC: 11756133. DOI: 10.1186/s13048-025-01591-9.

Feline coronavirus influences the biogenesis and composition of extracellular vesicles derived from CRFK cells.

Wijerathne S, Pandit R, Ipinmoroti A, Crenshaw B, Matthews Q Front Vet Sci. 2024; 11:1388438.

PMID: 39091390 PMC: 11292801. DOI: 10.3389/fvets.2024.1388438.

Melatonin and TGF-β-Mediated Release of Extracellular Vesicles.

Piekarska K, Bonowicz K, Grzanka A, Jaworski L, Reiter R, Slominski A Metabolites. 2023; 13(4).

PMID: 37110233 PMC: 10142249. DOI: 10.3390/metabo13040575.

References

Maas S, Breakefield X, Weaver A . Extracellular Vesicles: Unique Intercellular Delivery Vehicles. Trends Cell Biol. 2016; 27(3):172-188. PMC: 5318253. DOI: 10.1016/j.tcb.2016.11.003. View

Bernabeu C, Lopez-Novoa J, Quintanilla M . The emerging role of TGF-beta superfamily coreceptors in cancer. Biochim Biophys Acta. 2009; 1792(10):954-73. DOI: 10.1016/j.bbadis.2009.07.003. View

Barlow K, Sanders A, Soker S, Ergun S, Metheny-Barlow L . Pericytes on the tumor vasculature: jekyll or hyde?. Cancer Microenviron. 2012; 6(1):1-17. PMC: 3601214. DOI: 10.1007/s12307-012-0102-2. View

Kuriyama N, Yoshioka Y, Kikuchi S, Azuma N, Ochiya T . Extracellular Vesicles Are Key Regulators of Tumor Neovasculature. Front Cell Dev Biol. 2020; 8:611039. PMC: 7755723. DOI: 10.3389/fcell.2020.611039. View

Simeone P, Bologna G, Lanuti P, Pierdomenico L, Guagnano M, Pieragostino D . Extracellular Vesicles as Signaling Mediators and Disease Biomarkers across Biological Barriers. Int J Mol Sci. 2020; 21(7). PMC: 7178048. DOI: 10.3390/ijms21072514. View

OLoghlen A . Role for extracellular vesicles in the tumour microenvironment. Philos Trans R Soc Lond B Biol Sci. 2017; 373(1737). PMC: 5717441. DOI: 10.1098/rstb.2016.0488. View

Cao M, Seike M, Soeno C, Mizutani H, Kitamura K, Minegishi Y . MiR-23a regulates TGF-β-induced epithelial-mesenchymal transition by targeting E-cadherin in lung cancer cells. Int J Oncol. 2012; 41(3):869-75. PMC: 3582905. DOI: 10.3892/ijo.2012.1535. View

Wu F, Weigel K, Zhou H, Wang X . Paradoxical roles of TGF-β signaling in suppressing and promoting squamous cell carcinoma. Acta Biochim Biophys Sin (Shanghai). 2017; 50(1):98-105. PMC: 5846704. DOI: 10.1093/abbs/gmx127. View

Hao Y, Baker D, Ten Dijke P . TGF-β-Mediated Epithelial-Mesenchymal Transition and Cancer Metastasis. Int J Mol Sci. 2019; 20(11). PMC: 6600375. DOI: 10.3390/ijms20112767. View

10.

Massam-Wu T, Chiu M, Choudhury R, Chaudhry S, Baldwin A, McGovern A . Assembly of fibrillin microfibrils governs extracellular deposition of latent TGF beta. J Cell Sci. 2010; 123(Pt 17):3006-18. PMC: 2923573. DOI: 10.1242/jcs.073437. View

11.

Yoshimatsu Y, Watabe T . Emerging roles of inflammation-mediated endothelial-mesenchymal transition in health and disease. Inflamm Regen. 2022; 42(1):9. PMC: 8818500. DOI: 10.1186/s41232-021-00186-3. View

12.

Korn C, Augustin H . Mechanisms of Vessel Pruning and Regression. Dev Cell. 2015; 34(1):5-17. DOI: 10.1016/j.devcel.2015.06.004. View

13.

Liu S, Ren J, Ten Dijke P . Targeting TGFβ signal transduction for cancer therapy. Signal Transduct Target Ther. 2021; 6(1):8. PMC: 7791126. DOI: 10.1038/s41392-020-00436-9. View

14.

Sherwood E, Toliver-Kinsky T . Mechanisms of the inflammatory response. Best Pract Res Clin Anaesthesiol. 2004; 18(3):385-405. DOI: 10.1016/j.bpa.2003.12.002. View

15.

Gonzalo-Gil E, Galindo-Izquierdo M . Role of transforming growth factor-beta (TGF) beta in the physiopathology of rheumatoid arthritis. Reumatol Clin. 2014; 10(3):174-9. DOI: 10.1016/j.reuma.2014.01.009. View

16.

Chen L, Deng H, Cui H, Fang J, Zuo Z, Deng J . Inflammatory responses and inflammation-associated diseases in organs. Oncotarget. 2018; 9(6):7204-7218. PMC: 5805548. DOI: 10.18632/oncotarget.23208. View

17.

Ma J, Sanchez-Duffhues G, Goumans M, Ten Dijke P . TGF-β-Induced Endothelial to Mesenchymal Transition in Disease and Tissue Engineering. Front Cell Dev Biol. 2020; 8:260. PMC: 7187792. DOI: 10.3389/fcell.2020.00260. View

18.

Yates A, Pink R, Erdbrugger U, Siljander P, Dellar E, Pantazi P . In sickness and in health: The functional role of extracellular vesicles in physiology and pathology in vivo: Part I: Health and Normal Physiology: Part I: Health and Normal Physiology. J Extracell Vesicles. 2022; 11(1):e12151. PMC: 8765331. DOI: 10.1002/jev2.12151. View

19.

Wu F, Yang J, Liu J, Wang Y, Mu J, Zeng Q . Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer. Signal Transduct Target Ther. 2021; 6(1):218. PMC: 8190181. DOI: 10.1038/s41392-021-00641-0. View

20.

Kalluri R, Weinberg R . The basics of epithelial-mesenchymal transition. J Clin Invest. 2009; 119(6):1420-8. PMC: 2689101. DOI: 10.1172/JCI39104. View