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Molecular Diagnostics

Large tumour-derived extracellular vesicles as prognostic indicators of metastatic cancer patient survival

Abstract

Extracellular vesicles (EVs) are released by all cells and produced at particularly high levels by many cancer cells, often inducing pro-tumorigenic effects. Since these cancer EVs carry tumour proteins and RNAs, they can potentially be used at biomarkers. The heterogeneity of surface markers and cargos carried by EVs, however, presents some challenges to developing such approaches. Nanou et al. [1] found that automated counting of large tumour-derived EVs (tdEVs) performed at least as effectively as counting circulating tumour-derived cells (CTCs) and with higher sensitivity, in distinguishing the survival of patients with castration-resistant prostate cancer (CRPC), metastatic colorectal cancer (mCRC) and metastatic breast cancer (MBC), but not for non-small cell lung cancer (NSCLC). Subsequent work has suggested that these tdEVs may also be used to assess tumour subtype and that the number of large EVs produced by endothelial cells can also be increased in cancer patients. While by itself, the tdEV imaging approach used by Nanou et al. [1] is not specific enough to predict the survival of individual patients, in combination with other EV-associated assays, this test, perhaps enhanced through the inclusion of other tumour antigens, could prove invaluable in predicting cancer survival and other outcomes in the clinic.

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Fig. 1: Production of different types of EVs from cancer cells.

References

  1. Nanou A, Miller MC, Zeune LL, de Wit S, Punt CJA, Groen HJM, et al. Tumour-derived extracellular vesicles in blood of metastatic cancer patients associate with overall survival. Br J Cancer. 2020;122:801–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. van Niel G, Carter DRF, Clayton A, Lambert DW, Raposo G, Vader P. Challenges and directions in studying cell-cell communication by extracellular vesicles. Nat Rev Mol Cell Biol. 2022;23:369–82.

    Article  PubMed  Google Scholar 

  3. Meehan B, Rak J, Di Vizio D. Oncosomes—large and small: what are they, where they came from? J Extracell Vesicles. 2016;5:33109.

    Article  PubMed  Google Scholar 

  4. Cheng L, Hill AF. Therapeutically harnessing extracellular vesicles. Nat Rev Drug Discov. 2022;21:379–99.

    Article  CAS  PubMed  Google Scholar 

  5. Chen G, Huang AC, Zhang W, Zhang G, Wu M, Xu W, et al. Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. Nature. 2018;560:382–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Poggio M, Hu T, Pai CC, Chu B, Belair CD, Chang A, et al. Suppression of exosomal PD-L1 induces systemic anti-tumor immunity and memory. Cell. 2019;177:414–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Wortzel I, Dror S, Kenific CM, Lyden D. Exosome-mediated metastasis: communication from a distance. Dev Cell. 2019;49:347–60.

    Article  CAS  PubMed  Google Scholar 

  8. Al-Nedawi K, Meehan B, Micallef J, Lhotak V, May L, Guha A, et al. Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat Cell Biol. 2008;10:619–24.

    Article  CAS  PubMed  Google Scholar 

  9. Ciardiello C, Leone A, Lanuti P, Roca MS, Moccia T, Minciacchi VR, et al. Large oncosomes overexpressing integrin alpha-V promote prostate cancer adhesion and invasion via AKT activation. J Exp Clin Cancer Res. 2019;38:317.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Weng J, Xiang X, Ding L, Wong AL, Zeng Q, Sethi G, et al. Extracellular vesicles, the cornerstone of next-generation cancer diagnosis? Semin Cancer Biol. 2021;74:105–120.

    Article  CAS  PubMed  Google Scholar 

  11. Jiang C, Fu Y, Liu G, Shu B, Davis J, Tofaris GK. Multiplexed profiling of extracellular vesicles for biomarker development. Nanomicro Lett 2021;14:3.

    PubMed  PubMed Central  Google Scholar 

  12. Hoshino A, Kim HS, Bojmar L, Gyan KE, Cioffi M, Hernandez J, et al. Extracellular vesicle and particle biomarkers define multiple human cancers. Cell. 2020;182:1044–1061.e18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Tian Y, Gong M, Hu Y, Liu H, Zhang W, Zhang M, et al. Quality and efficiency assessment of six extracellular vesicle isolation methods by nano-flow cytometry. J Extracell Vesicles. 2020;9:1697028.

    Article  CAS  PubMed  Google Scholar 

  14. Crescitelli R, Lässer C, Lötvall J. Isolation and characterization of extracellular vesicle subpopulations from tissues. Nat Protoc 2021;16:1548–80.

    Article  CAS  PubMed  Google Scholar 

  15. Hilton SH, White IM. Advances in the analysis of single extracellular vesicles: A critical review. Sens Actuators Rep. 2021;3:100052.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Larson CJ, Moreno JG, Pienta KJ, Gross S, Repollet M, O’hara SM, et al. Apoptosis of circulating tumor cells in prostate cancer patients. Cytom A. 2004;62:46–53.

    Article  Google Scholar 

  17. Coumans FAW, Doggen CJM, Attard G, de Bono JS, Terstappen LWMM. All circulating EpCAM+CK+CD45- objects predict overall survival in castration-resistant prostate cancer. Ann Oncol. 2010;21:1851–7.

    Article  CAS  PubMed  Google Scholar 

  18. Nanou A, Coumans FAW, van Dalum G, Zeune LL, Dolling D, Onstenk W, et al. Circulating tumor cells, tumor-derived extracellular vesicles and plasma cytokeratins in castration-resistant prostate cancer patients. Oncotarget. 2018;9:19283–93.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Dathathri E, Isebia KT, Abali F, Lolkema MP, Martens JWM, Terstappen LWMM, et al. Liquid biopsy based circulating biomarkers in metastatic prostate cancer. Front Oncol. 2022;12:863472.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Nanou A, Zeune LL, Bidard FC, Pierga JY, Terstappen LWMM. HER2 expression on tumor-derived extracellular vesicles and circulating tumor cells in metastatic breast cancer. Breast Cancer Res. 2020b;22:86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Nanou A, Mol L, Coumans FAW, Koopman M, Punt CJA, Terstappen LWMM. Endothelium-derived extracellular vesicles associate with poor prognosis in metastatic colorectal cancer. Cells. 2020c;9:2688.

    Article  CAS  PubMed Central  Google Scholar 

  22. Yoh KE, Lowe CJ, Mahajan S, Suttmann R, Nguy T, Reichelt M, et al. Enrichment of circulating tumor-derived extracellular vesicles from human plasma. J Immunol Methods. 2021;490:112936.

    Article  CAS  PubMed  Google Scholar 

  23. Shiromizu T, Kume H, Ishida M, Adachi J, Kano M, Matsubara H, et al. Quantitation of putative colorectal cancer biomarker candidates in serum extracellular vesicles by targeted proteomics. Sci Rep. 2017;7:12782.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Lin AA, Nimgaonkar V, Issadore D, Carpenter EL. Extracellular vesicle-based multianalyte liquid biopsy as a diagnostic for cancer. Annu Rev Biomed Data Sci. 2022;5:269–92.

    Article  PubMed  Google Scholar 

  25. Théry C, Witwer KW, Aikawa E, Alcaraz MJ, Anderson JD, Andriantsitohaina R, et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J Extracell Vesicles. 2018;7:1535750.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Witwer KW, Goberdhan DC, O’Driscoll L, Théry C, Welsh JA, Blenkiron C, et al. Updating MISEV: Evolving the minimal requirements for studies of extracellular vesicles. J Extracell Vesicles. 2021;10:e12182.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kowal J, Arras G, Colombo M, Jouve M, Morath JP, Primdal-Bengtson B, et al. Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes. Proc Natl Acad Sci. 2016;113:E968–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Fan SJ, Kroeger B, Marie PP, Bridges EM, Mason JD, McCormick K, et al. Glutamine deprivation alters the origin and function of cancer cell exosomes. EMBO J. 2020;39:e103009.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

DCIG acknowledges Prof. Clive Wilson for helpful discussions. This work was supported by a Cancer Research UK Programme Award (C19591/A19076), Cancer Research UK Primer Award (C19591/A28123) and a BBSRC Project Award (BB/R004862/1).

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DCIG designed the work leading to the submission, drafted and revised the manuscript, approved the final version and agrees to be accountable for all aspects of this work.

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Correspondence to Deborah C. I. Goberdhan.

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Goberdhan, D.C.I. Large tumour-derived extracellular vesicles as prognostic indicators of metastatic cancer patient survival. Br J Cancer (2022). https://doi.org/10.1038/s41416-022-02055-3

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