Biomedical Engineering Reference
In-Depth Information
it is easier to establish a colon-cancer stem cell culture from more advanced
stage colorectal cancers, indicating that the cancer stem cells in these cancers
may have become independent of a stem cell niche factor that is absent from the
currently used culture media. However, this remains speculation to date.
The in vitro differentiated cells lose the capacity to initiate a carcinoma upon
injection into mice. This exemplifies the intriguing consequence of the cancer
stem cell model that genetically identical cells can have a completely diverse
malignant potential. It is to date unknown if the more differentiated cells
can revert back and adopt cancer stem cell capacities when exposed to de-
differentiating signals. This seems unlikely in vitro since only the cancer stem
cells characterized by CD133 expression can give rise to a colon-cancer stem cell
culture. Moreover the experiments that involve direct cell sorting from CRCs
show that if there is any de-differentiation present it is not a frequent event in
these settings. However, this could be completely different in an established
tumor that contains a putative colon-cancer stem cell niche.
6 Origin of the Colon-Cancer Stem Cell
Cancer stem cells have been defined as cells that (1) are able to self-renew and
(2) give rise to the variety of differentiated cells present in a malignancy.
However, it is not necessarily required that these cells are derived from a normal
tissue-specific stem cell. In this respect the name 'cancer stem cell' can, and does,
cause confusion and the alternative term 'tumor-initiating cell' might be better
suited. However, the latter term implies that this cell was the cell that initiated
the malignancy. This is not the case as there is clear evidence that the cancer
stem cell compartment can undergo changes during the progression of the
neoplasm. An additional problem with the term cancer stem cell is that it does
not cover the adenoma stage during which clonal expansion begins. This
problem can be solved by distinguishing the adenoma stem cell from the cancer
stem cell and considering an adenoma to cancer stem cell model of colorectal
cancer.
Although not necessary to fulfill the criteria to be called a cancer stem cell,
there is some circumstantial evidence that in fact the colonic stem cells are the
cells that acquire the various genetic hits to develop a CRC. The first argument
is the long period a stem cell is believed to reside in the colonic crypts. Colonic
stem cells are predicted to spend
20 years in the human body. The turnover of
the more differentiated cells is believed to be completed every 7 days in the adult
colon. So, in theory it is much more likely for the stem cells to be subject to
acquiring malignancy-inducing genetic alterations. A good alternative, how-
ever, is for a genetic change to cause a more committed precursor cell to (re)gain
stem cell-like properties. As differentiated cells are much more abundant in the
colon, this could potentially compensate for the fact that the stem cells reside in
the body much longer. It is therefore even possible that mutations in more
