Biomedical Engineering Reference
In-Depth Information
3D-differentiation is reported using matrigel (a viscous mixture of extracellular
matrix compounds). The in vitro differentiated cells lose expression of colon-
cancer stem cell markers, such as CD133, and gain expression of differentiation
markers (Fig. 2).
More importantly, the described colon-cancer stem cell cultures have the
capacity to induce tumors in mice upon subcutaneous injection. These tumors
exhibit a differentiated morphology together with preservation of a functional
cancer stem cell compartment. This illustrates that the colon-cancer stem cell
capacities have been retained during the period the cells were expanded in vitro.
This is unique since normal CRC-derived cell lines, i.e., cultured in serum-
containing medium on adherent plastics, can be tumorigenic upon subcuta-
neous injection in mice but result in an undifferentiated mass of cells (Weinberg,
2007; Fig 3). In glioblastoma it has been shown that the gene expression profiles
of the cancer stem cell cultures, and derived xenografts, resemble the expression
pattern of the original malignancy much more closely than do the classical
adherent cell lines and their xenografts (Lee et al., 2006). In addition, the
number of genetic alterations observed in the glioblastoma cancer stem cell
was much lower than those observed in regular glioblastoma cell lines. Com-
bined, these data suggest that cancer stem cell cultures are a culture system that
is superior to traditional cancer cell lines irrespective of the cancer stem cell
theory. However, care is warranted since the success rate of establishing a
colon-cancer stem cell culture is limited (25-50%); evidently this results in a
selection of malignancies, used for in vitro research, that contain a cancer stem
cell compartment that can proliferate under the described culture conditions.
This might indicate that the tumors that cannot be cultured efficiently in vitro
contain cancer stem cells which are dependent on certain (growth) factors that
are not present in the used medium. In this respect it is interesting to realize that
Fig. 3 (a) Typical histology of a colorectal adenocarcinoma. The epithelial cells form crypt-
like structures surrounded by stromal cells. (b) Subcutaneous injection of colon-cancer
spheroid cultures results in a tumor with a morphology that is similar to the original primary
human malignancy. Note also the presence of stroma in the tumor. (c) Subcutaneous injection
of a classical colon-cancer cell line, in this case HT29, results in an undifferentiated tumor
mass. In those xenografts the typical morphology that characterizes colorectal cancers are
mostly lost
