Refining the role for adult stem cells as cancer cells of origin - PubMed (original) (raw)
Review
Refining the role for adult stem cells as cancer cells of origin
Andrew C White et al. Trends Cell Biol. 2015 Jan.
Abstract
Significant progress has been made to identify the cells at the foundation of tumorigenesis, the cancer cell of origin (CCO). The majority of data points towards resident adult stem cells (ASCs) or primitive progenitors as the CCO for those cancers studied, highlighting the importance of stem cells not only as propagators but also as initiators of cancer. Recent data suggest tumor initiation at the CCOs can be regulated through both intrinsic and extrinsic signals and that the identity of the CCOs and their propensity to initiate tumorigenesis is context dependent. In this review, we summarize some of the recent findings regarding CCOs and solid tumor initiation and highlight its relation with bona fide human cancer.
Keywords: cancer cells of origin; genetic hits; stem cell niche; tumor initiation.
Copyright © 2014 Elsevier Ltd. All rights reserved.
Figures
Figure 1
Typical ASC hierarchy. Within most mature tissues, a hierarchy exists where cell turnover is controlled first by a self-renewing ASC. These relatively quiescent cells give rise to TACs. TACs go through several rounds of division and then immediately differentiate to form the various specialized cells of the tissue. The delicate balance of cell fate decisions summarized in this figure are typically controlled by well-known signaling pathways (such as Wnt, Tgf, Bmp, Shh, and Fgf) acting through both autocrine and paracrine mechanisms. ASC, adult stem cell; TAC, transient amplifying cell.
Figure 2
Tumor initiation scenarios and factors that can affect them. (A) Based on the existing literature, there are several scenarios by which tumor initiation could occur in the cell types of the stem cell hierarchy. Retrospective pathological studies have suggested that differentiated cells can initiate cancers, while prospective approaches to the study of cancer initiation using molecular genetics suggest that either stem or transit-amplifying cells are more relevant. (B) Data in various tissues proposes models whereby tumor initiation in unperturbed tissue follows scenario A. However, upon induction of dramatic changes to the microenvironment of tumor initiation, CCOs do not necessarily follow a typical stem cell hierarchy. There are several examples where terminally specified cells can dedifferentiate to create a cell that adopts stem cell properties and is thus able to become a CCO. (C) Changes to the signaling microenvironment can also affect tumor initiation. The same signaling pathways that are known to drive development of tissues are also implicated in tumor initiation and progression. For example, in the prostate, when stromal Tgfβ signaling is reduced, HGF is induced in the epithelium, leading to proliferation. In addition, upregulated expression of Fgf10 and Hmga2 in the meschyme can lead to increased androgen receptor signaling and Wnt signaling in the adjacent epithelium (respectively), again leading to abnormal epithelial proliferation. These cases are demonstrative of microenvironmental aberrations that can potentially enhance or induce epithelial cancer. CCO, cancer cell of origin; Fgf10, fibroblast growth factor 10; HGF, hepatocyte growth factor; Hmga2,
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