Biomedical Engineering Reference
In-Depth Information
Cancer Stem Cells in Colorectal Cancer
Louis Vermeulen, Jan Paul Medema, James C.H. Hardwick,
and Gijs R. van den Brink
Abstract Colorectal cancer is the second most common cause of cancer death
in the Western world. Due to the high prevalence of colorectal cancer and
precancerous lesions, many colonoscopies, and the resulting wide availability
of tissue samples, extensive knowledge is available on the stepwise process that
leads to colorectal cancer. Most colorectal cancers develop from slowly growing
non-invasive adenomas that take many years to grow from a single mutant
crypt to an adenoma that can reach several centimeters in size before acquiring
invasive characteristics. In this chapter we will discuss some of the early histo-
pathological events in the development of colorectal cancer and try to reconcile
these data with the concept of the tumor-initiating or cancer stem cell. We will
show that there are many similarities between the mechanism of stem cell
expansion during intestinal growth and repair and deregulated clonal expan-
sion of stem cells in an adenoma. We argue that it is important to realize the fact
that most known genetic alterations in colorectal cancer development are
involved in adenoma formation and are therefore involved in clonal growth
and not invasiveness. It would therefore be helpful to distinguish adenoma stem
cells from carcinoma stem cells. We will then discuss the available data on the
isolation and behavior of colorectal cancer stem cells.
Contents
1
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
224
2 Normal Colon Stem Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
225
2.1
Identification of Colonic Stem Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
225
2.2 Morphogenetic Pathways Regulate Colonic Epithelial Cell Fate . . . . . . . . .
226
2.3 Clonal Stem Cell Expansion in Colonic Epithelial
Damage and Repair . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
229
3 Colorectal Carcinogenesis and Origin of the Colon-Cancer
Stem Cell . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
230
G.R.van den Brink (*)
Department of Gastroenterology & Hepatology, Leiden University Medical Center,
Leiden, The Netherlands
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