Skip to main content

Quantitative Identification of Senescent Cells in Cancer

  • Protocol
  • First Online:
Cancer Immunosurveillance

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1884))

Abstract

Cellular senescence, a state of permanent growth arrest, is an important mechanism preventing the propagation of damaged cells. It suppresses cancer development in premalignant lesions in response to activated oncogenes and in tumors following therapy. The presence of senescent cells in premalignant lesions and tumors is controlled by the immune system. The ability to identify and quantify senescent cells more efficiently in vivo is necessary in order to evaluate the effect of these cells on tumorigenesis and cancer therapy. Through combining senescent-associated beta-galactosidase staining with ImageStream X analysis, we have developed an effective method to identify and quantify senescent cancer cells in vivo.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Collado M, Serrano M (2010) Senescence in tumours: evidence from mice and humans. Nat Rev Cancer 10(1):51–57. https://doi.org/10.1038/nrc2772

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Narita M, Lowe SW (2005) Senescence comes of age. Nat Med 11(9):920–922

    Article  CAS  Google Scholar 

  3. Schmitt CA, Fridman JS, Yang M, Lee S, Baranov E, Hoffman RM, Lowe SW (2002) A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy. Cell 109(3):335–346

    Article  CAS  Google Scholar 

  4. Serrano M, Lin AW, McCurrach ME, Beach D, Lowe SW (1997) Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88(5):593–602

    Article  CAS  Google Scholar 

  5. Schmitt CA (2007) Cellular senescence and cancer treatment. Biochim Biophys Acta 1775(1):5–20. https://doi.org/10.1016/j.bbcan.2006.08.005

    Article  CAS  PubMed  Google Scholar 

  6. Lujambio A, Akkari L, Simon J, Grace D, Tschaharganeh DF, Bolden JE, Zhao Z, Thapar V, Joyce JA, Krizhanovsky V, Lowe SW (2013) Non-cell-autonomous tumor suppression by p53. Cell 153(2):449–460. https://doi.org/10.1016/j.cell.2013.03.020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Kang TW, Yevsa T, Woller N, Hoenicke L, Wuestefeld T, Dauch D, Hohmeyer A, Gereke M, Rudalska R, Potapova A, Iken M, Vucur M, Weiss S, Heikenwalder M, Khan S, Gil J, Bruder D, Manns M, Schirmacher P, Tacke F, Ott M, Luedde T, Longerich T, Kubicka S, Zender L (2011) Senescence surveillance of pre-malignant hepatocytes limits liver cancer development. Nature 479(7374):547–551. https://doi.org/10.1038/nature10599

    Article  CAS  PubMed  Google Scholar 

  8. Krizhanovsky V, Yon M, Dickins RA, Hearn S, Simon J, Miething C, Yee H, Zender L, Lowe SW (2008) Senescence of activated stellate cells limits liver fibrosis. Cell 134(4):657–667

    Article  CAS  Google Scholar 

  9. Sagiv A, Burton DG, Moshayev Z, Vadai E, Wensveen F, Ben-Dor S, Golani O, Polic B, Krizhanovsky V (2016) NKG2D ligands mediate immunosurveillance of senescent cells. Aging 8(2):328–344. https://doi.org/10.18632/aging.100897

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Biran A, Perelmutter M, Gal H, Burton DG, Ovadya Y, Vadai E, Geiger T, Krizhanovsky V (2015) Senescent cells communicate via intercellular protein transfer. Genes Dev 29(8):791–802. https://doi.org/10.1101/gad.259341.115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Sagiv A, Biran A, Yon M, Simon J, Lowe SW, Krizhanovsky V (2013) Granule exocytosis mediates immune surveillance of senescent cells. Oncogene 32(15):1971–1977. https://doi.org/10.1038/Onc.2012.206

    Article  CAS  PubMed  Google Scholar 

  12. te Poele RH, Okorokov AL, Jardine L, Cummings J, Joel SP (2002) DNA damage is able to induce senescence in tumor cells in vitro and in vivo. Cancer Res 62(6):1876–1883

    Google Scholar 

  13. Dimri GP, Lee X, Basile G, Acosta M, Scott G, Roskelley C, Medrano EE, Linskens M, Rubelj I, Pereira-Smith O, Peacocke M, Campisi J (1995) A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci U S A 92(20):9363–9367

    Article  CAS  Google Scholar 

  14. Biran A, Zada L, Abou Karam P, Vadai E, Roitman L, Ovadya Y, Porat Z, Krizhanovsky V (2017) Quantitative identification of senescent cells in aging and disease. Aging Cell 16(4):661–671. https://doi.org/10.1111/acel.12592

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This work was supported by grants to V.K. from the European Research Council under the European Union’s FP7 and from the Israel Science Foundation; and staff scientist internal grant from the Weizmann Institute of Science to Z.P. V.K. is an incumbent of the Karl and Frances Korn Career Development Chair in Life Sciences.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Ziv Porat or Valery Krizhanovsky .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Biran, A., Porat, Z., Krizhanovsky, V. (2019). Quantitative Identification of Senescent Cells in Cancer. In: López-Soto, A., Folgueras, A. (eds) Cancer Immunosurveillance. Methods in Molecular Biology, vol 1884. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8885-3_18

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-8885-3_18

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-8884-6

  • Online ISBN: 978-1-4939-8885-3

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics