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.
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References
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
Narita M, Lowe SW (2005) Senescence comes of age. Nat Med 11(9):920–922
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
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
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
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
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
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
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
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
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
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
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
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
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.
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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
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DOI: https://doi.org/10.1007/978-1-4939-8885-3_18
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