Location, location, location: the cancer stem cell niche

Abstract

The existence of a stem cell niche, or physiological microenvironment, consisting of specialized cells that directly and indirectly participate in stem cell regulation has been verified for mammalian adult stem cells in the intestinal, neural, epidermal, and hematopoietic systems. In light of these findings, it has been proposed that a "cancer stem cell niche" also exists and that interactions with this tumor niche may specify a self-renewing population of tumor cells. We discuss emerging data that support the idea of a veritable cancer stem cell niche and propose several models for the relationship between cancer cells and their niches.

Figure 1. Models for the Relationship between Cancer Stem Cells and Their Niches

An activated niche providing necessary factors (shown as red circles) for expansion and self-renewal is depicted in blue, whereas a quiescent niche lacking such factors is depicted in green. (A) Normal and CaSC niches may be one and the same. CaSCs may be activated in response to cues from the normal stem cell niche. (B) An activated niche may precede the advent of the CaSC. CaSCs may be dependent on the pre-existence of a favorable niche for expansion. (C) CaSCs may provide signals (purple arrow) that instruct an otherwise quiescent niche to become activated. (D) Signals from the CaSCs (blue arrow) may result in amplification of the activated niche, permitting further expansion of the tumor. (E) CaSCs may be niche independent. That is, they may acquire the ability to cell-autonomously provide the necessary factors for expansion and self-renewal that are normally restricted by the niche. (F) An inhibitory niche, shown in purple, may exist as distinct from the normal or CaSC-activating niches. In this case, signals from the niche shut down the CaSCs, inducing differentiation or death.