Colon Cancer
Stem Cells Causing "Breathless
Excitement"
by David W. Sharp
Medicine
Top Ten
Papers
Rank
Papers
Cites
Jul-Aug
08
Rank
May-Jun
08
1
J. Yu, et
al., "Induced
pluripotent stem
cell lines derived
from human somatic
cells,"
Science,
318(5858): 1917-20,
21 December 2007.
[Genome Ctr.
Wisconsin, Madison;
U. Wisconsin,
Madison] *243HE
89
2
2
B. Escudier, et
al.,
"Sorafenib in
advanced clear-cell
renal-cell
carcinoma," New
Engl. J. Med.,
356(2): 125-34, 11
January 2007. [15
institutions
worldwide] *124NE
75
8
3
S.E. Nissen, K.
Wolski, "Effect of
rosiglitazone on
the risk of
myocardial
infarction and
death from
cardiovascular
causes," New
Engl. J. Med.,
356(24): 2457-71,
14 June 2007.
[Cleveland Clinic,
OH] *178DR
69
1
4
R.J. Motzer, et
al.,
"Sunitinib versus
interferon alfa in
metastatic
renal-cell
carcinoma," New
Engl. J. Med.,
356(2): 115-24, 11
January 2007. [10
institutions
worldwide] *124NE
63
3
5
R. Sladek, et
al., "A
genome-wide
association study
identifies novel
risk loci for type
2
diabetes,"
Nature,
445(7130):
881-5, 22
February 2007.
[14
institutions
worldwide]
*138CR
46
5
6
E. Zeggini, et
al.,
"Replication of
genome-wide
association signals
in UK samples
reveals risk loci
for type 2
diabetes,"
Science,
316(5829): 1336-41,
1 June 2007. [10
U.K. institutions]
*173PS
41
7
7
L.J. Scott, et
al., "A
genome-wide
association study
of type 2 diabetes
in Finns detects
multiple
susceptibility
variants,"
Science,
316(5829): 1341-5,
1 June 2007. [12
U.S. and Finland
institutions]
*173PS
40
4
8
V.
Schächinger,
et al.,
"Intracoronary bone
marrow-derived
progenitor cells in
acute myocardial
infarction,"
New Engl. J.
Med., 355(12):
1210-21, 21
September 2006. [10
German and Swiss
institutions]
*085IT
39
†
9
C.A. O'Brien,
et al., "A
human colon cancer
cell capable of
initiating tumour
growth in
immunodeficient
mice,"
Nature,
445(7123): 106-10,
4 January 2007.
[University Health
Network, Toronto,
Canada; Mount Sinai
Hosp., Toronto; U.
Toronto] *122KG
39
†
10
L. Ricci-Vitiani,
et al.,
"Identification and
expansion of human
colon-cancer-initiating
cells,"
Nature,
445(7123): 111-5, 4
January 2007. [Ist.
Super. Sanita,
Rome, Italy;
Mediterranean Inst.
Oncol., Catania,
Italy; U. La
Sapienza, Rome; U.
Palermo, Italy]
*122KG
In his very recent review of the importance of
stem-cell ideas to cancer
research, Prof. John E. Dick, University of Toronto,
Canada, (who kindly provided Science Watch
with early access) notes that it is not just
research articles and reviews but also funding
bodies that are "making strong predictions that
targeting CSCs (cancer stem cells) more effectively
will lead to improved patient outcomes"
(Blood, 112[13]: 4793-807, 2008). Indeed,
there is a "breathless excitement" about this shift
in thinking—though here, one suspects, Prof.
Dick is trying to introduce a note of caution. His
own special area of interest is in the leukemias,
but it is research on a solid tumor that brings the
Toronto group and also an Italian team into the Top
Ten this time (#9, #10).
The notion that there might be CSCs is not new, and
confirmation of their existence has been emerging. Both
Catherine O’Brien (#9) and Lucia Ricci-Vitiani
(#10) and their colleagues were trying to find out, for
colon cancer, if all cancer cells have the potential to
initiate and then sustain the growth of tumors or
whether those properties are restricted to some
identifiable subfraction of cells. If it is the latter,
then that cell subset ought to be a good target for
novel and better-directed treatments.
Using xenotransplantation into immunodeficient mice,
O’Brien et al. found that all cells
capable of initiating colon cancer were positive for
the cell marker CD133 but not all CD133-positive cells
possess this property. The cancer-initiating cells were
more than 200 times as frequent in the CD133-positive
subset than in unfractionated tumor cells (1 in
57,000). All the same, they were rare (1 in 262), so
more refined studies are required to narrow down their
identity. The Italian group’s methodology and
conclusions are very similar.
CD133 must have seemed well-deserving of its 2008
designation in the Journal of Pathology as
"molecule of the moment" (D. Mizrak, M. Brittan, M.R.
Alison, J Pathol., 214[1]; 3-9, 2008).
However, a paper in the Journal of Clinical
Investigation last summer appeared to cast some
doubt on the role of CD133 cells. The title says it
all: "CD133 expression is not restricted to stem cells,
and both CD133+ and CD133- metastatic colon cancer
cells initiate tumors" (S.V. Shmelkov, et al.,
J. Clin. Invest., 118[6]: 2111-20, 2008). Of
course, the work highlighted in this issue of
Science Watch (#9, #10) is not saying that
only stem cells are expressing CD133; it is the number
of locations where CD133 is expressed that is
surprising in Shmelkov and colleagues’ report. In
a balanced commentary on the Shmelkov et al.
paper, Mark A. LaBarge and Mina J. Bissell, from the
Lawrence Berkeley National Laboratory, California,
(J. Clin. Invest., 118[6]:2021-4, 2008) note
that metastatic cancer cells may behave differently, so
the fact that such cells can initiate tumors even
though they are CD133 negative may not be contradicting
the findings of O’Brien, Ricci-Vitiani, and their
colleagues.
Do differences in colon-cancer-inducing cells have
prognostic value? Recent work (D. Horst, et
al., Brit. J. Cancer, 99[8]:1285-9, 2008)
suggests that they might, for CD133 anyway. Samples
from 77 patients with colon cancer were divided into
two groups, those highly positive for CD133 (more than
50% of cells positive) and those less positive.
Survival analysis revealed that patients who were
highly positive had a worse outcome.
A former deputy editor of The Lancet,
Mr. David W. Sharp, M.A. (Cambridge), is a freelance
writer living in Minchinhampton, Gloucestershire,
U.K.
Keywords: cancer stem cells, CSCs, John E. Dick,
Catherine O’Brien, Lucia Ricci-Vitiani, colon
cancer, CD133, stem cells.