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. Issue 10 (19th May 2017)

• Record Type: Journal Article
• Authors: Murakami, Takashi; Hiroshima, Yukihiko; Miyake, Kentaro; Hwang, Ho Kyoung; Kiyuna, Tasuku; DeLong, Jonathan C.; Lwin, Thinzar M.; Matsuyama, Ryusei; Mori, Ryutaro; Kumamoto, Takafumi; Chishima, Takashi; Tanaka, Kuniya; Ichikawa, Yasushi; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M.
• Is Part Of: Cell cycle. Volume 16:Issue 10(2017)
• Page Start: 1008
• Page End: 1014
• Publication Date: 2017-05-19
• Subjects: BxPC-3 -- cancer cells -- color-coded intravital imaging -- GFP -- orthotopic mouse model -- pancreatic cancer -- RFP -- stromal cells -- TGF-β inhibitor; Cell cycle -- Periodicals; 571.84377
• DOI: 10.1080/15384101.2017.1315489
• Languages: English
• ISSNs: 1538-4101

Abstract

ABSTRACT: 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.