Biomedical Engineering Reference
In-Depth Information
antigen (PSA) and prostatic acid phosphatase (PAP) and are the majority of
cells found within both normal and hyperplastic epithelium. They express low-
molecular weight cytokeratins, such as K8 and K18, and (Sar et al. 1990) and
are androgen-dependent (Kyprianou and Isaacs 1988). In contrast, the basal
cells are less differentiated, do not secrete PSA or PAP, express p63 and high-
molecular weight cytokeratins (K5 and K14), have low to undetectable levels of
AR, and are androgen-independent (Kyprianou and Isaacs 1988). There are
some cells that express a phenotype intermediate between basal and luminal in
that they express K5, K8, and K18 but not K14 (Verhagen et al. 1992).
The identification of SCs in the prostate was first demonstrated by English
et al.(1987) in rats using androgen cycling experiments where the prostate
involutes upon androgen withdrawal and regenerates with return of androgen.
They determined that cells within the basal layer contained the cells for regen-
erating the prostate, i.e., the stem cells. Isaacs and Coffey (1989) proposed the
existence of long-lived SCs that are androgen-independent and give rise to the
androgen-responsive transit-amplifying cells that in turn produce the andro-
gen-dependent secretory luminal cells. It was further demonstrated that basal
cells that rapidly adhere to type I collagen are both clonogenic (Xin et al. 2005;
Collins et al. 2001) and capable of forming prostate-like glands in immunocom-
promised mice (Collins et al. 2001). Several in vitro studies revealed that
prostatic basal epithelial cells can give rise to luminal cells (Liu et al. 1997;
Robinson et al. 1998; Tran et al. 2002). Mice that are null for p63, a basal cell
marker, are born without a prostate, providing compelling evidence that the SC
is part of the basal component (Signoretti et al. 2000, 2005). In the case of
prostatic CSCs, several groups have reported that the cells displaying SC
characteristics are AR negative and express basal cytokeratins (Collins et al.
2005; Richardson et al. 2004; Patrawala et al. 2006).
However, there also exists evidence that the prostatic SCmay have a TA or even
a luminal cell origin. Since the majority of cells present in prostate cancers are of the
luminal type and there are often very few detectable basal cells in adenocarcinomas,
it was suggested that prostate cancers most often arise from a luminal cell (Nagle
et al. 1987). It was suggested that intermediate TA cells that have regained the
ability to self-renew are responsible for the generation of prostate cancer (van
Leenders and Schalken 2001). Others showed the prostatic SCs may not be limited
to the basal compartment. Long-term BrdU label retention experiments label cells
of both basal and luminal origin even after several cycles of androgen ablation,
suggesting that the SC is not restricted to the basal layer (Tsujimura et al. 2002).
3 Identification and Isolation of Cancer Stem Cells
The first step in understanding these cells is to definitively identify them. The
isolation of prostate CSCs has taken three major approaches. Two of the
approaches, side populations (SP) and sphere formation, are based on biological
