Biomedical Engineering Reference
In-Depth Information
When a CSC is transplanted in an immunocompromisedmouse, self-renewal and
pluripotency are vital for the formation of a tumor that recapitulates the original
(reviewed in Wang and Dick 2005). In addition, long-term self-renewal capacity
can be measured by serially transplanting the purified CSC population over
several generations (reviewed in Huntly and Gilliland 2005). The result is the
continual recapitulation of the original tumor phenotype.
Having a high proliferative capacity helps a SC maintain a tissue or tumor. It is
worth noting that self-renewal and proliferation are not the same. Self-renewal is a
unique cell division that enables the SC to maintain its high proliferative and
differentiation capacity as the parental SC (reviewed in Al-Hajj and Clarke
2004). This quality is of particular relevance during hematopoietic development.
Work done by Morrison and Weissman (1994) showed that multipotent progeni-
tor cells recapitulated mature blood cells in lethally irradiated mice but they were
unable to maintain the system for more than 2 months. The injected cells became
more differentiated and lost their ability to proliferate. In contrast, hematopoietic
SCs were able to recapitulate the blood system for the life of the animal. In
addition, these SCs were serially transplanted into lethally irradiated mice and
continued to maintain the hematopoietic system. The SCs maintained their high
proliferative capacity and ability to self-renew. CSCs and normal SCs share the
ability to self-renew and maintain the capacity to proliferate extensively. They are
the putative population responsible for generation and maintenance of a hetero-
geneous population of cells. Breast cancer was the first example of a solid tumor
found to have CSCs. As little as 100 breast CSCs formed tumors in a murine
xenograft model (Al-Hajj et al. 2003). Furthermore, these cancer SCs were able to
recapitulate the tumor when serially transplanted into NOD/SCIDmice up to four
passages. The vast majority of cells isolated from the tumors appeared to be transit-
amplifying and/or terminally differentiated cells and these cells were unable to
generate a tumor. Presumably with every cell division, the transit-amplifying cell
became more differentiated and eventually lost its proliferative capacity.
In summary, the existence of CSCs and their ability to differentiate into
multiple lineages, self-renew, and high proliferative capacity makes them parti-
cularly insidious to the nature of oncogenesis, malignancy, tumor recurrence,
and therapies that do not target these cells. These tumor-initiating cells are the
tumorigenic force behind tumor initiation, growth, metastasis, drug resistance,
and relapse (reviewed in Pardal et al. 2003).
2 The Cell of Origin of Normal and Cancerous Prostatic StemCells
The cellular origin of the prostatic SC is still under debate. There are several
lines of evidence that the normal prostate SC has a basal phenotype (reviewed in
Collins and Maitland 2006). The prostate epithelium is composed of two
morphologically distinct layers, the basal and luminal. These layers are further
composed of three types of cells: basal, secretory luminal, and neuroendocrine.
The luminal cells are terminally differentiated cells that secrete prostate-specific
