The Role of Extracellular Vesicles in Metabolic Reprogramming of the Tumor Microenvironment

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2022 May 14

PMID 35563739

Authors

Eran S Fridman

Lana Ginini

Ziv Gil

Affiliations

Soon will be listed here.

Abstract

The tumor microenvironment (TME) includes a network of cancerous and non-cancerous cells, together with associated blood vessels, the extracellular matrix, and signaling molecules. The TME contributes to cancer progression during various phases of tumorigenesis, and interactions that take place within the TME have become targets of focus in cancer therapy development. Extracellular vesicles (EVs) are known to be conveyors of genetic material, proteins, and lipids within the TME. One of the hallmarks of cancer is its ability to reprogram metabolism to sustain cell growth and proliferation in a stringent environment. In this review, we provide an overview of TME EV involvement in the metabolic reprogramming of cancer and stromal cells, which favors cancer progression by enhancing angiogenesis, proliferation, metastasis, treatment resistance, and immunoevasion. Targeting the communication mechanisms and systems utilized by TME-EVs is opening a new frontier in cancer therapy.

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References

Muller L, Simms P, Hong C, Nishimura M, Jackson E, Watkins S . Human tumor-derived exosomes (TEX) regulate Treg functions via cell surface signaling rather than uptake mechanisms. Oncoimmunology. 2017; 6(8):e1261243. PMC: 5593709. DOI: 10.1080/2162402X.2016.1261243. View

Pavlides S, Whitaker-Menezes D, Castello-Cros R, Flomenberg N, Witkiewicz A, Frank P . The reverse Warburg effect: aerobic glycolysis in cancer associated fibroblasts and the tumor stroma. Cell Cycle. 2009; 8(23):3984-4001. DOI: 10.4161/cc.8.23.10238. View

Zhang J, Song F, Zhao X, Jiang H, Wu X, Wang B . EGFR modulates monounsaturated fatty acid synthesis through phosphorylation of SCD1 in lung cancer. Mol Cancer. 2017; 16(1):127. PMC: 5518108. DOI: 10.1186/s12943-017-0704-x. View

Fischer K, Hoffmann P, Voelkl S, Meidenbauer N, Ammer J, Edinger M . Inhibitory effect of tumor cell-derived lactic acid on human T cells. Blood. 2007; 109(9):3812-9. DOI: 10.1182/blood-2006-07-035972. View

Alharbi M, Lai A, Sharma S, Kalita-de Croft P, Godbole N, Campos A . Extracellular Vesicle Transmission of Chemoresistance to Ovarian Cancer Cells Is Associated with Hypoxia-Induced Expression of Glycolytic Pathway Proteins, and Prediction of Epithelial Ovarian Cancer Disease Recurrence. Cancers (Basel). 2021; 13(14). PMC: 8305505. DOI: 10.3390/cancers13143388. View

Cianciaruso C, Beltraminelli T, Duval F, Nassiri S, Hamelin R, Mozes A . Molecular Profiling and Functional Analysis of Macrophage-Derived Tumor Extracellular Vesicles. Cell Rep. 2019; 27(10):3062-3080.e11. PMC: 6581796. DOI: 10.1016/j.celrep.2019.05.008. View

de Araujo Farias V, OValle F, Serrano-Saenz S, Anderson P, Andres E, Lopez-Penalver J . Exosomes derived from mesenchymal stem cells enhance radiotherapy-induced cell death in tumor and metastatic tumor foci. Mol Cancer. 2018; 17(1):122. PMC: 6094906. DOI: 10.1186/s12943-018-0867-0. View

Ghanem N, El-Baba C, Araji K, El-Khoury R, Usta J, Darwiche N . The Pentose Phosphate Pathway in Cancer: Regulation and Therapeutic Opportunities. Chemotherapy. 2021; 66(5-6):179-191. DOI: 10.1159/000519784. View

Skog J, Wurdinger T, van Rijn S, Meijer D, Gainche L, Sena-Esteves M . Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol. 2008; 10(12):1470-6. PMC: 3423894. DOI: 10.1038/ncb1800. View

10.

Wang D, Zhao C, Xu F, Zhang A, Jin M, Zhang K . Cisplatin-resistant NSCLC cells induced by hypoxia transmit resistance to sensitive cells through exosomal PKM2. Theranostics. 2021; 11(6):2860-2875. PMC: 7806469. DOI: 10.7150/thno.51797. View

11.

Gubin M, Zhang X, Schuster H, Caron E, Ward J, Noguchi T . Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens. Nature. 2014; 515(7528):577-81. PMC: 4279952. DOI: 10.1038/nature13988. View

12.

Zhang D, Vu L, Ismail N, Le M, Grimson A . Landscape of extracellular vesicles in the tumour microenvironment: Interactions with stromal cells and with non-cell components, and impacts on metabolic reprogramming, horizontal transfer of neoplastic traits, and the emergence of therapeutic.... Semin Cancer Biol. 2021; 74:24-44. DOI: 10.1016/j.semcancer.2021.01.007. View

13.

Wang X, Zhang H, Yang H, Bai M, Ning T, Deng T . Exosome-delivered circRNA promotes glycolysis to induce chemoresistance through the miR-122-PKM2 axis in colorectal cancer. Mol Oncol. 2020; 14(3):539-555. PMC: 7053238. DOI: 10.1002/1878-0261.12629. View

14.

Sousa C, Biancur D, Wang X, Halbrook C, Sherman M, Zhang L . Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion. Nature. 2016; 536(7617):479-83. PMC: 5228623. DOI: 10.1038/nature19084. View

15.

Boussadia Z, Lamberti J, Mattei F, Pizzi E, Puglisi R, Zanetti C . Acidic microenvironment plays a key role in human melanoma progression through a sustained exosome mediated transfer of clinically relevant metastatic molecules. J Exp Clin Cancer Res. 2018; 37(1):245. PMC: 6173926. DOI: 10.1186/s13046-018-0915-z. View

16.

Margolis L, Sadovsky Y . The biology of extracellular vesicles: The known unknowns. PLoS Biol. 2019; 17(7):e3000363. PMC: 6667152. DOI: 10.1371/journal.pbio.3000363. View

17.

Liu J, Peng X, Yang S, Li X, Huang M, Wei S . Extracellular vesicle PD-L1 in reshaping tumor immune microenvironment: biological function and potential therapy strategies. Cell Commun Signal. 2022; 20(1):14. PMC: 8796536. DOI: 10.1186/s12964-021-00816-w. View

18.

Chen F, Chen J, Yang L, Liu J, Zhang X, Zhang Y . Extracellular vesicle-packaged HIF-1α-stabilizing lncRNA from tumour-associated macrophages regulates aerobic glycolysis of breast cancer cells. Nat Cell Biol. 2019; 21(4):498-510. DOI: 10.1038/s41556-019-0299-0. View

19.

Zhang X, Liu Z, Hou Y, Jiao H, Ren J, Wang G . EV PD-L1 Contributes to Immunosuppressive CD8 T Cells in Peripheral Blood of Pediatric Wilms Tumor. Technol Cancer Res Treat. 2021; 20:15330338211041264. PMC: 8445529. DOI: 10.1177/15330338211041264. View

20.

Li J, Wu X, Schiffmann L, MacVicar T, Zhou C, Wang Z . IL-17B/RB Activation in Pancreatic Stellate Cells Promotes Pancreatic Cancer Metabolism and Growth. Cancers (Basel). 2021; 13(21). PMC: 8611647. DOI: 10.3390/cancers13215338. View