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Origin of Cancer Stem Cells: The Role of Self-Renewal and Differentiation

Tianjin Medical University Cancer Institute and Hospital, Ti-Yuan-Bei, Huan-Hu-Xi Road, He-Xi District, Tianjin, 300060, China

Correspondence: Address correspondence and reprint requests to: Xiong-Zhi Wu, PhD; E-mail: ilwxz{at}163.com

Background: Self-renewal and differentiation potential is the feature of stem cells. Differentiation is usually considered to be a one-way process of specialization as cells develop the functions of their ultimate fate and lose their immature characteristics, such as self-renewal. Progenitor cells, the products of stem cells losing the activity of self-renewal, could differentiate to mature cells, which have the feature of differentiation and lose the activity of self-renewal. The roles for cancer stem cells have been demonstrated for some cancers. However, the origin of the cancer stem cells remains elusive.

Methods: This review focuses on current scientific controversies related to the establishment of the cancer stem cells — in particular, how self-renewal and differentiation block might contribute to the evolution of cancer.

Results: Cancer stem cells may be caused by transforming mutations occurring in multi-potential stem cells, tissue-specific stem cells, progenitor cells, mature cells and cancer cells. Progenitor cells obtain the self-renewal activity by activating the self-renewal-associated genes rather than dedifferentiate to tissue special stem cells. The transform multi-potential stem cells gain the differentiation feature of special tissue by differentiating to cancer cells. Mature cells and cancer cells may dedifferentiate or reprogram to cancer stem cells by genetic and / or epigenetic events to gain the self-renewal activity and lose some features of differentiation. The cancer-derived stem cells are not the "cause", but the "consequence" of carcinogenesis. The genetic program controlling self-renewal and differentiation is a key unresolved issue.

Conclusion: Cancer stem cells may be caused by disturbance of self-renewal and differentiation occurring in multi-potential stem cells, tissue-specific stem cells, progenitor cells, mature cells and cancer cells.

Key Words: Cancer stem cell • Carcinogenesis • Differentiation • Progenitor cell • Self-renewal