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Review
. 2005 Jan;7(1):17-23.
doi: 10.1016/j.ccr.2004.12.013.

Context, tissue plasticity, and cancer: are tumor stem cells also regulated by the microenvironment?

Mina J Bissell  1 , Mark A Labarge
Affiliations
Review

Context, tissue plasticity, and cancer: are tumor stem cells also regulated by the microenvironment?

Mina J Bissell et al. Cancer Cell. 2005 Jan.
No abstract available

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Figures

Figure 1
Figure 1. A normal microenvironment can preserve the tissue architecture even in the presence of predisposed cells, and an aberrant microenvironment can promote the mutated cells to form tumors
Normal (blue) and genetically damaged (yellow) tissue-specific stem cells are shown in their niche surrounded by an instructive microenvironment that is composed of cellular (stroma), structural (ECM molecules), and soluble components (growth factors, cytokines, proteases, and hormones, among others). Normal and damaged TSSC can regenerate and replenish their respective tissues of origin in response to normal microenvironmental cues (blue solid and yellow dashed arrows). However, when balanced control over the TSSCs is altered, they can also give rise to tumors (yellow solid arrows). Cells in the cap region of the virgin rodent mammary gland, and those in upper basal region of the ducts and possibly acini, thought by some to be the physical location of the mammary stem cells, can give rise to both luminal and myoepithelial cells during development and lactation (Williams and Daniel, 1983); others assert that the TSSCs are located throughout the gland (Smith and Boulanger, 2002). The same signals that promote normal stem cell activity could push a predisposed stem cell to initiate carcinoma of the breast. The skeletal muscle stem cell is shown in its characteristic satellite cell position; however, reports have also shown that they may reside in interstitial spaces. Normally, during times of muscle regeneration, they fuse with muscle fibers to provide new myonuclei, but under rare circumstances, they are thought to give rise to rhabdomyosarcomas (Keller et al., 2004; Tiffin et al., 2003). Skin stem cells residing in the bulge region give rise to the root sheathe during the hair cycle, but in some cases are thought to be the origin of basal cell carcinomas (Owens and Watt, 2003). The ependymal cells of the subventricular zone (SVZ) in the CNS normally give rise to astrocytes, neurons, and oligodendrocytes. Under some conditions, however, they are known as the cause of ependycytomas or astrocytomas (Maher et al., 2001).
Figure 2
Figure 2. Integration of signaling pathways by the microenvironment
The important element to consider here is that the normal microenvironment must integrate what is correct (tissue-specific functions, differentiation) by giving the pathways involved the green light, but also prevent what is wrong (pathways for inappropriate growth, apoptosis, and cancer). When the microenvironment becomes aberrant, the opposite will happen: the normal differentiated state is blocked and those pathways that were blocked previously now become operative.
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