Color-coded intravital imaging demonstrates a transforming growth factor-?
(TGF-?) antagonist selectively targets stromal cells in a human pancreatic-cancer
orthotopic mouse model
#MMPMID28441080
Murakami T
; Hiroshima Y
; Miyake K
; Hwang HK
; Kiyuna T
; DeLong JC
; Lwin TM
; Matsuyama R
; Mori R
; Kumamoto T
; Chishima T
; Tanaka K
; Ichikawa Y
; Bouvet M
; Endo I
; Hoffman RM
Cell Cycle
2017[May]; 16
(10
): 1008-1014
PMID28441080
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Pancreatic cancer is a recalcitrant malignancy, partly due to desmoplastic stroma
which stimulates tumor growth, invasion, and metastasis, and inhibits
chemotherapeutic drug delivery. Transforming growth factor-? (TGF-?) has an
important role in the formation of stromal desmoplasia. The present study
describes the ability of color-coded intravital imaging to demonstrate the
efficacy of a TGF-? inhibitor to target stroma in an orthotopic mouse model of
pancreatic cancer. The BxPC-3 human pancreatic adenocarcinoma cell line
expressing green fluorescent protein (GFP), which also has a high TGF-?
expression level, was used in an orthotopic model in transgenic nude mice
ubiquitously expressing red fluorescent protein (RFP). Fourteen mice were
randomized into a control group (n = 7, vehicle, i.p., weekly, for 3 weeks) and a
treated group (n = 7, SB431542 [TGF-? receptor type I inhibitor] 0.3 mg, i.p.,
weekly, for 3 weeks). Stromal cells expressing RFP and cancer cells expressing
GFP were observed weekly for 3 weeks by real-time color-coded intravital imaging.
The RFP fluorescence area from the stromal cells, relative to the GFP
fluorescence area of the cancer cells, was significantly decreased in the
TGF-?-inhibitor-treatment group compared to the control group. The present study
demonstrated color-coded imaging in an orthotopic pancreatic-cancer cell-line
mouse model can readily detect the selective anti-stromal-cell targeting of a
TGF-? inhibitor.
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