Prostate Cancer Stem Cells - Stem Cells and Cancer - page 149

were also CD133 + (Richardson et al. 2004). Furthermore, they showed that the
CD133-positive cells are restricted to the a2b1 hi cells. The a2b1 hi CD133 + cells
were capable of regenerating prostate like acini in immunocompromised mice
and demonstrated a high proliferative potential in vitro (Richardson et al.
2004).
Another basal cell marker, CD44, was also reported to mark prostate stem
cells (Liu et al. 1997). Liu et al. demonstrated that CD44 + prostate epithelial
cells when co-cultured with stromal cells in the presence of Matrigel and
androgen were capable of producing PSA, a luminal marker. This presumably
occurred through differentiation, although it was not formally proven.
3.3.2 Prostate Cancer Stem Cell Markers
Using cell lines, Patrawala et al. demonstrated that purified CD44 + cells exhib-
ited important properties of CSCs, such as (1) long-term retention of BrdU
indicating that the cells are relatively quiescent, (2) initiation of tumors at low
numbers (100 cells), (3) the tumors could be serially transplanted, and (4) were
maintained in cell culture for extended periods of time (Patrawala et al. 2006;
Tang et al. 2007). However, it was these authors who concluded that the CD44 +
population was still a heterogeneous population that was enriched for CSCs.
Working with patient primary samples, Collins et al. demonstrated
CD44 + CD133 + integrin-a2b1 hi cells had higher proliferation rates and invasive
potentials compared with CD133-negative cells. This population represented
approximately 0.1% of tumor cells, independent of Gleason grade. Further-
more, these cells could differentiate into AR-positive cells and cells that reca-
pitulated the original tumor phenotype in in vitro differentiation cultures. The
tumorigenic capacities of these cells were not tested, which is often considered a
vital element in proving that the cells under investigation are indeed CSCs.
However, using the DU145 cell line, Chen et al. demonstrated that the
CD44 + CD133 + integrin-a2b1 hi cells are tumorigenic (Wei et al. 2007).
Also using cell lines, Hurt et al. (2008) demonstrated that rare
CD44 + CD24 cells (0.4% of the total population) are the tumorigenic cells.
Remarkably, when these cells were depleted from the total cell line, the remain-
ing cells did not initiate tumor formation. Furthermore, CD44 + CD24 cells
could be maintained in culture and tumors removed from immunocompro-
mised mice injected with 1000 CD44 + CD24 cells were phenotypically similar
to tumors removed from mice injected with 1 10 6 of the total cell line.
Importantly, it was demonstrated that these cells contained a molecular signa-
ture (termed the invasiveness gene signature, IGS) derived from breast CSCs
and predicted poor survival in not only breast cancer but prostate cancer
patients (Liu et al. 2007). Therefore, patients with a poor prognosis may indeed
have CSC-enriched tumors leading to an aggressive clinical course. Hurt et al.
also demonstrated that CD44 + CD24 contained higher levels of CD133
expression in comparison to the non-CSC population, such that this population
was in fact CD44 + CD24 CD133 + .