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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,a,b,c Yukihiko Hiroshima,c Kentaro Miyake,a,b,c Ho Kyoung Hwang,a,b Tasuku Kiyuna,a,b Jonathan C. DeLong,b Thinzar M. Lwin,b Ryusei Matsuyama,c Ryutaro Mori,c Takafumi Kumamoto,c Takashi Chishima,c Kuniya Tanaka,c Yasushi Ichikawa,c Michael Bouvet, M.D., FACS,b Itaru Endo, M.D., Ph.D.,c and Robert M. Hoffman, Ph.D.a,b 
 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. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실)
Yonsei Authors
황호경(Hwang, Ho Kyoung)
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