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Color-coded intravital imaging demonstrates a transforming growth factor-β (TGF-β) antagonist selectively targets stromal cells in a human pancreatic-cancer orthotopic mouse model

 Takashi Murakami  ;  Yukihiko Hiroshima  ;  Kentaro Miyake  ;  Ho Kyoung Hwang  ;  Tasuku Kiyuna  ;  Jonathan C. DeLong  ;  Thinzar M. Lwin  ;  Ryusei Matsuyama  ;  Ryutaro Mori  ;  Takafumi Kumamoto  ;  Takashi Chishima  ;  Kuniya Tanaka  ;  Yasushi Ichikawa  ;  Michael Bouvet  ;  Michael Bouvet  ;  Itaru Endo  ;  Robert M. Hoffman 
 Cell Cycle, Vol.16(10) : 1008-1014, 2017 
Journal Title
 Cell Cycle 
Issue Date
Animals ; Benzamides/administration & dosage* ; Cell Tracking/methods ; Dioxoles/administration & dosage* ; Disease Models, Animal ; Fluorescence ; Gene Expression Regulation, Neoplastic/genetics ; Green Fluorescent Proteins/genetics ; Humans ; Luminescent Proteins/genetics ; Mice ; Mice, Transgenic ; Pancreatic Neoplasms/diagnostic imaging ; Pancreatic Neoplasms/drug therapy* ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/pathology ; Stromal Cells/drug effects* ; Stromal Cells/pathology ; Transforming Growth Factor beta/antagonists & inhibitors ; Transforming Growth Factor beta/genetics* ; Tumor Microenvironment/drug effects
BxPC-3 ; GFP ; RFP ; TGF-β inhibitor ; cancer cells ; color-coded intravital imaging ; orthotopic mouse model ; pancreatic cancer ; stromal cells
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-β (TGF-β) 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-β 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-β 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-β 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-β-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-β inhibitor.
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1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
황호경(Hwang, Ho Kyoung) ORCID logo https://orcid.org/0000-0003-4064-7776
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