Identification of Human Cutaneous Squamous Cell Carcinoma Cancer Stem Cells

  • Carlotta Olivero
  • Huw Morgan
  • Girish K. PatelEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1879)


Epithelia are under constant threat from environmental carcinogens and none more so than squamous epithelia, which form the outermost linings of our bodies. Hence malignancies of squamous epithelia are collectively the most common cancer type and with the highest mortality, despite a constant cell turnover and only relatively rare long-lived adult tissue stem cells. Genetic analysis from SCC whole genome sequencing reveals commonality in mutated genes, despite various etiological factors. Most SCC types have been shown to exhibit hierarchical growth, in which a high frequency of cancer stem cells is associated with poor prognosis. For human cutaneous SCC (cSCC), we have shown that cancer stem cells express CD133 and that this population can recreate tumor heterogeneity in a novel in vivo model. CD133+ cSCC cells is small subset of tumor cells (~1%) in the outer layer of cSCC that are highly enriched for tumor-initiating capacity (TIC) (~1/400) compared to unsorted cSCC cells (~1/106). Xenografts of CD133+ cSCC recreated the original cSCC tumor histology and organizational hierarchy, while CD133- cells did not. Only CD133+ cells demonstrated the capacity for self-renewal in serial transplantation studies. Hence, cSCC has the potential to be the ideal model in which to study SCC biology.


Cancer stem cells Mouse models Skin cancer Squamous cell carcinoma Tumor-initiating cells 



This work is supported by grants from the Leo Foundation, Cancer Research UK, and Hywel Dda University Health Board.


  1. 1.
    Li YY, Hanna GJ, Laga AC, Haddad RI, Lorch JH, Hammerman PS (2015) Genomic analysis of metastatic cutaneous squamous cell carcinoma. Clin Cancer Res 21(6):1447–1456. Scholar
  2. 2.
    Pickering CR, Zhou JH, Lee JJ, Drummond JA, Peng SA, Saade RE et al (2014) Mutational landscape of aggressive cutaneous squamous cell carcinoma. Clin Cancer Res 20(24):6582–6592. Scholar
  3. 3.
    Patel GK, Yee CL, Yuspa SH, Vogel JC (2012) A humanized stromal bed is required for engraftment of isolated human primary squamous cell carcinoma cells in immunocompromised mice. J Invest Dermatol 132(2):284–290. Scholar
  4. 4.
    Cinzia Borgogna, Carlotta Olivero, Simone Lanfredini, Federica Calati, Marco De Andrea, Elisa Zavattaro et al (2018) β-HPV infection correlates with early stages of carcinogenesis in skin tumors and patient-derived Xenografts from a single center kidney transplant recipient cohort. Front Microbiol 9:117.
  5. 5.
    Patel GK, Yee CL, Terunuma A, Telford WG, Voong N, Yuspa SH, Vogel JC (2012) Identification and characterization of tumor-initiating cells in human primary cutaneous squamous cell carcinoma. J Invest Dermatol 132(2):401–409. Scholar
  6. 6.
    Olivero C, Lanfredini S, Borgogna C, Gariglio M, Patel GK (2018) HPV induced field cancerisation: transformation of adult tissue stem cell to cancer stem cell. Front Microbiol.
  7. 7.
    Herbst RS, Heymach JV, Lippman SM (2008) Lung cancer. N Engl J Med 359(13):1367–1380. Scholar
  8. 8.
    Forest VI, Clark JJ, Veness MJ, Milross C (2010) N1S3: a revised staging system for head and neck cutaneous squamous cell carcinoma with lymph node metastases: results of 2 Australian Cancer Centers. Cancer 116(5):1298–1304CrossRefGoogle Scholar
  9. 9.
    Vizcaino AP, Moreno V, Bosch FX et al (2000) International trends in incidence of cervical cancer: II squamous-cell carcinoma. Int J Cancer 86(3):429–435CrossRefGoogle Scholar
  10. 10.
    Zhang Y (2013) Epidemiology of esophageal cancer. World J Gastroenterol 19(34):5598–5606CrossRefGoogle Scholar
  11. 11.
    Mohan H, Bal A, Punia RP, Bawa AS (2003) Squamous cell carcinoma of the prostate. Int J Urol 10(2):114–116CrossRefGoogle Scholar
  12. 12.
    Ahmad I, Barnetson RJ, Krishna NS (2008) Keratinizing squamous metaplasia of the bladder: a review. Urol Int 81(3):247–251CrossRefGoogle Scholar
  13. 13.
    Syed MI, Stewart M, Syed S, Dahill S, Adams C, Mclellan DR, Clark LJ (2011) Squamous cell carcinoma of the thyroid gland: primary or secondary disease? J Laryngol Otol 125:3–9CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2018

Authors and Affiliations

  • Carlotta Olivero
    • 1
  • Huw Morgan
    • 1
  • Girish K. Patel
    • 1
    Email author
  1. 1.European Cancer Stem Cell Research InstituteCardiff UniversityCardiffUK

Personalised recommendations