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Cancer Stem Cells in Nasopharyngeal Carcinoma: Current Evidence
Fenggang Yu1, Kwok Seng Loh2
1
Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Head & Neck Tumor Group, National Cancer Institute of Singapore, National University Health System (NUHS), Singapore
Citation: Yu FG, Loh KS. Cancer stem cells in nasopharyngeal carcinoma: current evidence. J Nasopharyng
Carcinoma, 2014, 1(6): e6. doi:10.15383/jnpc.6.
Funding: This work was supported by a Grant from the National University Cancer Institute, Singapore (NCIS)
Centre Grant to Dr. Loh and Dr. Yu.
Competing interests: The authors have declared that no competing interests exist.
Conflict of interest: None.
Copyright:
article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use,
distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract: Nasopharyngeal carcinoma (NPC) is highly prevalent in southern China and Southeast Asia. Cancer
resistance to therapy, metastasis and disease recurrence are significant hurdles to successful treatment of NPC.
Identifying mechanisms by which NPC is resistantiscritical to improving patient survival. Evidence gathered in the
last decade suggests that tumor progression and recurrence may befuelled by cancer stem cells (CSCs).
Understanding how CSCs contribute to the pathology of NPC will potentiallyaid the pursuit of novel therapies. In
this review we summarize what major methods are currently used to identify CSCs in NPC and the challenges faced.
Keywords: Nasopharyngeal carcinoma; Cancer stem cells
Introduction
growth and heterogeneity[1]. In the first model, all tumor cells are
optimism.
but it was not until 1994, in their pioneer work, have John Dick
leukaemia malignant clone and defined the CSCs for the first
sustain
self-renewaland
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the
malignant
progeny
through
this paper, we will review the evidence for CSCs in NPC and the
various NPC cell lines. Overall, those studies support the evidence
Samples
BrdU
Refs
SP
about
[24]
[25]
1( 5-8F)
cells
CD44
total cells.
EBV+ NPC cell line C666-1 5.2861% of parental C666-1 cells are
cells
CD44+
And
C666-1 Spheroids
[27]
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tumors
Xenografts
Tissue sections from NPC 41 (39.0%) of 105 cases were defined as [28]
patients
ALDH1
EBV- NPC cell lines: 5-8F 1.96% of cells are ALDH1 positive
[29]
and CNE2
CD133
C666-1
[30]
CNE2
[31]
primary culture
state might account for the relapse in cancer patients that can
early study by Zhang et al.[23], the authors found there was about
sufficient
0.3% of label retaining cells (LRC) in NPC cell lines and their
glioblastomamultiforme
for
conferring
CSC
(GBM)[38],
phenotype,
thyroid
such
as
cancer[39],
functional assays[32,33,34].
cells
migration,tumor
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had
faster
proliferation,
formation
in
higher
mice,
clone
formation,
greaterstemness
gene
enrich for CSCs initially and they found the spheroid cells had at
CKIT, KLF4 and KLF5). Further work on CD44 showed that the
majority of spheroids cells are CD44+ and the CD44+ cells were
CD44-
primary
CD44
It is important to note that not only stem cells but also their transit-
the primary NPC cells. Does it mean there are actually no CSCs in
primary NPC cells orit is just an artificial adaption for C666-1 line
hierarchical
cells,
suggesting
tumors.
Serial
hierarchical
transplantation
relationship.
is
an
The
important
Although
CD133
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Unsolved Issues
cancer cells from brain, colon, lung, melanoma and other solid
Despite the useful data we obtained from the above studies, there
cells have stem cell or progenitor like properties and CD133 was
proposed as CSC marker[51]. Lun et al.[27]found that
The stem cell characteristics of CSCs beg the question of the cell
only observed very rare C666-1 cells with faint cytoplasmic but
that CSCs arise either from normal stem cells that have become
CSCs
xenograftsareneeded.
Basically, the above studies have demonstrated that NPC cells are
than the other to identify NPC CSCs. Even using the same cell
line and same marker [26,27], different results were obtained. The
exact reasons for the reported discrepancies across studies are not
colon
metastases in NPC[56,57,58].
al.[31]
3.360.35%CD133+
reported
evolution.
These
studies
cells
highlight
with
the
need
for
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80100% of
This suggests that EBV infection may not be the initiating event in
exclusively primary NPC cells are positive both for EBV and
chromosomal loss at
Figure 1.Primary cell culture of nasopharyngeal carcinoma (NPC). Primary NPC cells express EBV and basal cell markers revealed by immunohistochemistry with
antibodies against EBNA-1 and p63.
immunodeficient
and
formed one tumor out of six nude mice [27]. In our own study [30],
underestimated?
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mice[71,72].
By
contrast,
Morrison
Almost
all
NPC
cells
wereectopically
models[74,75] have been reported but it is not clear why it has not
there might be some CSCs which are very quiescent and survive
Are NPC Cscsquiescent Or Fast Proliferating?
select for fast proliferating cells? Are these fast proliferating cells
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found that Non-SP NPC cells can give rise to SP cells.We[30] also
there may exist more than one distinct cancer stem-like state
Yu.
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Conclusion
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