Prostate stem cell niche

In all epithelial organs, adult SCs are maintained in a tissue niche that regulates stem cell fate decisions. The niche provides structural support, as well as the biological cues that influence the SCs' decision to self-renew or divide into more differentiated progeny. Integrin and junctional proteins play a major role in regulating SC differentiation in the prostate [29]. For instance, integrin a6 shows a wider distribution amongst SC populations in the prostate tissue [28]. It was also shown that the high surface expression of a2pj integrin in human prostate epithelium correlates with colony forming ability and the potential to regenerate a fully differentiated prostate epithelium in vivo [25]. Additionally, proteins belonging to the connexin, cadherin and catenin families were reported as key molecules mediating cell-cell and cell-extracellular matrix interaction that dictate cell differentiation decisions [30].

Prostate homeostasis is maintained as a result of androgenic regulation of stromal epithelial interactions. Mesenchyme is the key androgen target tissue during development of prostate and many androgenic effects expressed in epithelium are elucidated trough paracrine influences from the mesenchyme [31].

The pathways controlling SC fate in prostate include NOTCH1 and Transforming growth factor beta-1 (TGFp1) signaling. NOTCH signaling is critical for normal cell proliferation and differentiation in the prostate, and deregulation of this pathway may facilitate prostatic oncogenesis [32]. Increased TGFp1 signaling has been found in the quiescent proximal region of the ducts in an androgen-replete animal and cells in this region were also overex-pressing the B-cell leukemia/lymphoma-2 (Bcl-2) protein, which protects them from apoptosis [33]. This signaling seems to be responsible for a quiescent stem cell niche.

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