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2015 ; 106
(9
): 1182-7
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Susceptibility of pancreatic cancer stem cells to reprogramming
#MMPMID26298849
Noguchi K
; Eguchi H
; Konno M
; Kawamoto K
; Nishida N
; Koseki J
; Wada H
; Marubashi S
; Nagano H
; Doki Y
; Mori M
; Ishii H
Cancer Sci
2015[Sep]; 106
(9
): 1182-7
PMID26298849
show ga
Previous reports have indicated that reprogramming technologies may be useful for
altering the malignant phenotype of cancer cells. Although somatic stem cells in
normal tissues are more sensitive to reprogramming induction than differentiated
cells, it remains to be elucidated whether any specific subpopulations are
sensitive to reprogramming in heterogeneous tumor tissues. Here we examined the
susceptibility of pancreatic cancer stem cells (CSC) and non-CSC to
reprogramming. To characterize CSC populations, we focused on c-Met signaling,
which has been identified as a marker of CSC in mouse experiments in vivo. Cells
that expressed high levels of c-Met showed higher CSC properties, such as
tumor-initiating capacity, and resistance to gemcitabine. Real-time reverse
transcription-polymerase chain reaction in cells expressing high levels of c-Met
revealed endogenous expression of reprogramming factors, such as OCT3/4, SOX2,
KLF4 and cMYC. Introduction of these four factors resulted in higher alkaline
phosphatase staining in cells with high c-Met expression than in controls.
Therefore, the study results demonstrate that cellular reprogramming may be
useful for extensive epigenetic modification of malignant features of pancreatic
CSC.
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