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Tumour-initiating stem-like cells in human prostate cancer exhibit increased NF-κB signalling

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  • Vinagolu K. Rajasekhar

    (Stem Cell Center and Developmental Biology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center
    Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center)

  • Lorenz Studer

    (Stem Cell Center and Developmental Biology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center)

  • William Gerald

    (Memorial Sloan-Kettering Cancer Center)

  • Nicholas D. Socci

    (Computational Biology Center, Memorial Sloan-Kettering Cancer Center)

  • Howard I. Scher

    (Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center)

Abstract

Androgen depletion is a key strategy for treating human prostate cancer, but the presence of hormone-independent cells escaping treatment remains a major therapeutic challenge. Here, we identify a minor subset of stem-like human prostate tumour-initiating cells (TICs) that do not express prostate cancer markers, such as androgen receptor or prostate specific antigen. These TICs possess stem cell characteristics and multipotency as demonstrated by in vitro sphere-formation and in vivo tumour-initiation, respectively. The cells represent an undifferentiated subtype of basal cells and can be purified from prostate tumours based on coexpression of the human pluripotent stem cell marker TRA-1-60 with CD151 and CD166. Such triple-marker-positive TICs recapitulate the original parent tumour heterogeneity in serial xeno-transplantations indicating a tumour cell hierarchy in human prostate cancer development. These TICs exhibit increased nuclear factor-κB activity. These findings are important in understanding the molecular basis of human prostate cancer.

Suggested Citation

  • Vinagolu K. Rajasekhar & Lorenz Studer & William Gerald & Nicholas D. Socci & Howard I. Scher, 2011. "Tumour-initiating stem-like cells in human prostate cancer exhibit increased NF-κB signalling," Nature Communications, Nature, vol. 2(1), pages 1-13, September.
    • Handle: RePEc:nat:natcom:v:2:y:2011:i:1:d:10.1038_ncomms1159
    DOI: 10.1038/ncomms1159
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    1. Hong Yuen Wong & Quanhu Sheng & Amanda B. Hesterberg & Sarah Croessmann & Brenda L. Rios & Khem Giri & Jorgen Jackson & Adam X. Miranda & Evan Watkins & Kerry R. Schaffer & Meredith Donahue & Elizabet, 2022. "Single cell analysis of cribriform prostate cancer reveals cell intrinsic and tumor microenvironmental pathways of aggressive disease," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    2. Laura Solé & Teresa Lobo-Jarne & Daniel Álvarez-Villanueva & Josune Alonso-Marañón & Yolanda Guillén & Marta Guix & Irene Sangrador & Catalina Rozalén & Anna Vert & Antonio Barbachano & Joan Lop & Mar, 2022. "p53 wild-type colorectal cancer cells that express a fetal gene signature are associated with metastasis and poor prognosis," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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