The isolation and characterization of cancer associated fibroblasts for clinical therapeutic application.

2013 Fiscal Year Final Research Report

• Project/Area Number: 23791549
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Kumamoto University
• Principal Investigator: OKABE Hirohisa 熊本大学, 医学部附属病院, 非常勤診療医師 (40573621)
• Project Period (FY): 2011 – 2013
• Keywords: CAF（癌関連線維芽細胞） / 胆管癌

Research Abstract

The aim of this study is to isolate cancer-associated fibroblasts (CAFs) and characterize them in cholangiocarcinoma. In addition, we aimed to isolate normal fibroblasts to find the difference from CAFs considering therapeutic application. Since the tissue of human cholanigocarcinoma was quite difficult to digest and the number of patients was limited, we decided to get myofibroblasts form chronic inflammatory liver and normal fibroblasts from normal liver using mouse model. We performed liver perfusion and optimized the digestion buffer. We made the protocol of cell separation for both populations.

Research Products

• [Journal Article] Role of leukocyte cell-derived chemotaxin 2 as a biomarker in hepatocellular carcinoma (2014)
  • Author(s): Okabe H, Delgado E, Lee JM, Yang J, Kinoshita H, Hayashi H, Tsung A, Behari J, Beppu T, Baba H, Monga SP.
  • Journal Title: Plos One Volume: (in press)
  • Peer Reviewed
• [Journal Article] Beta-catenin signaling in murine liver zonation and regeneration : A Wnt-Wnt situation! (2014)
  • Author(s): Yang J, Nejak-Bowen KN, Okabe H, Lang RA, Williams RO, Monga SP.
  • Journal Title: Hepatology 2014 Volume: (in press)
  • DOI: 10.1002/hep.27082
  • Peer Reviewed
• [Journal Article] Rank classification based on the combination of indocyanine green retention rate at 15 min and (99m)Tc-DTPA-galactosyl human serum albumin scintigraphy predicts the safety of hepatic resection (2014)
  • Author(s): Okabe H, Beppu T, Hayashi H, Masuda T, Mima K, Nakagawa S, Kuroki H, Imai K, Nitta H, Masuda T, Hashimoto D, Chikamoto A, Wanatanabe M, Ishiko T, Yoshida M, Yamashita Y, Baba H.
  • Journal Title: Nucl Med Commun Volume: 35 Pages: 478-483
  • DOI: 10.1097/MNM.0000000000000075
  • Peer Reviewed
• [Journal Article] Macrophage-derived reactive oxygen species suppress miR-328 targeting CD44 in cancer cells and promote redox adaptation (2014)
  • Author(s): Ishimoto T, Sugihara H, Watanabe M, Sawayama H, Iwatsuki M, Baba Y, Okabe H, Hidaka K, Yokoyama N, Miyake K, Yoshikawa M, Nagano O, Komohara Y, Takeya M, Saya H, Baba H.
  • Journal Title: Carcinogenesis Volume: 35(5) Pages: 1003-11
  • DOI: 10.1093/carcin/bgt402
  • Peer Reviewed
• [Journal Article] CD44s signals the acquisition of the mesenchymal phenotype required for anchorage-independent cell survival in hepatocellular carcinoma (2014)
  • Author(s): Okabe H, Ishimoto T, Mima K, Nakagawa S, Hayashi H, Kuroki H, Imai K, Nitta H, Saito S, Hashimoto D, Chikamoto A, Ishiko T, Watanabe M, Nagano O, Beppu T, Saya H, Baba H.
  • Journal Title: Br J Cancer Volume: 110(4) Pages: 958-66
  • DOI: 10.1038/bjc.2013.759
  • Peer Reviewed
• [Journal Article] Remnant liver volume-based predictors of postoperative liver dysfunction after hepatectomy : Analysis of 625 consecutive patients from a single institution (2013)
  • Author(s): Okabe H, Beppu T, Chikamoto A, Hayashi H, Yoshida M, Masuda T, Imai K, Mima K, Nakagawa S, Kuroki H, Nitta H, Hashimoto D, Ishiko T, Yamashita Y, Baba H.
  • Journal Title: Int J Clin Oncol Volume: (Epub ahead of print)
  • DOI: 10.1007/s10147-013-0591-0
  • Peer Reviewed
• [Journal Article] Percentage of future liver remnant volume before portal vein embolization influences the degree of liver regeneration after hepatectomy. J Gastrointest Surg (2013)
  • Author(s): Okabe H, Beppu T, Nakagawa S, Yoshida M, Hayashi H, Masuda T, Imai K, Mima K, Kuroki H, Nitta H, Hashimoto D, Chikamoto A, Ishiko T, Watanabe M, Yamashita Y, Baba H.
  • Journal Title: J Gastrointest Surg Volume: 17(8) Pages: 1447-51
  • DOI: 10.1007/s11605-013-2237-y
  • Peer Reviewed
• [Journal Article] CD44v6 expression is related to mesenchymal phenotype and poor prognosis in patients with colorectal cancer (2013)
  • Author(s): Saito S, Okabe H, Watanabe M, Ishimoto T, Iwatsuki M, Baba Y, Tanaka Y, Kurashige J, Miyamoto Y, Baba H.
  • Journal Title: Oncol Rep Volume: 29 Pages: 1570-1578
  • DOI: 10.3892/or.2013.2273
  • Peer Reviewed
• [Journal Article] Epithelial-mesenchymal transition expression profiles as a prognostic factor for disease-free survival in hepatocellular carcinoma : Clinical significance of transforming growth factor-βsignaling (2013)
  • Author(s): Mima K, Hayashi H, Kuroki H, Nakagawa S, Okabe H, Chikamoto A, Watanabe M, Beppu T, Baba H.
  • Journal Title: Oncol Lett Volume: 5 Pages: 149-154
  • DOI: 10.3892/ol.2012.954
  • Peer Reviewed
• [Journal Article] High CD44s expression is associated with the EMT expression profile and intrahepatic dissemination of hepatocellular carcinoma after local ablation therapy (2013)
  • Author(s): Mima K, Hayashi H, Imai K, Kuroki H, Nakagawa S, Okabe H, Chikamoto A, Watanabe M, Beppu T, Baba H.
  • Journal Title: J Hepatobiliary Pancreat Sci Volume: 20(4) Pages: 429-34
  • DOI: 10.1007/s00534-012-0580-0
  • Peer Reviewed
• [Journal Article] CYLD downregulation is correlated with tumor development in patients with hepatocellular carcinoma (2013)
  • Author(s): Kinoshita H, Okabe H, Beppu T, Chikamoto A, Hayashi H, Imai K, Mima K, Nakagawa S, Yokoyama N, Ishiko T, Shinriki S, Jono H, Ando Y, Baba H.
  • Journal Title: Mol Clin Oncol Volume: 1 Pages: 309-314
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/24649166
  • Peer Reviewed
• [Journal Article] Cystine/glutamic acid transporter (xCT) is a novel marker for predicting poor survival in patients with hepatocellular carcinoma (2013)
  • Author(s): Kinoshita H, Okabe H, Beppu T, Chikamoto A, Hayashi H, Imai K, Mima K, Nakagawa S, Ishimoto T, Miyake K, Yokoyama N, Ishiko T, Baba H.
  • Journal Title: Oncol Rep Volume: 29 Pages: 685-689
  • DOI: 10.3892/or.2012.2162
  • Peer Reviewed
• [Journal Article] Upregulation of ERCC1 and DPD expressions after oxaliplatin based first-line chemotherapy for metastatic colorectal cancer (2012)
  • Author(s): Baba H, Watanabe M, Okabe H, Miyamoto Y, Sakamoto Y, Baba Y, Iwatsuki M, Chikamoto A, Beppu T.
  • Journal Title: Br J Cancer Volume: 107 Pages: 1950-1955
  • DOI: 10.1038/bjc.2012.502
  • Peer Reviewed
• [Journal Article] Esternal biliary drainage and liver regeneration after major hepatectomy (2012)
  • Author(s): Otao R, Beppu T, Ishiko T, Mima K, Okabe H, Hayashi H, Masuda T, Chikamoto A, Takamori H, Baba H.
  • Journal Title: Br J Surg Volume: 99 Pages: 1569-74
  • DOI: 10.1002/bjs.8906
  • Peer Reviewed
• [Journal Article] CD44s regulates the TGF-β-mediated mesenchymal phenotype and is associated with poor prognosis in patients with hepatocellular carcinoma (2012)
  • Author(s): Mima K, Okabe H, Ishimoto T, Hayashi H, Nakagawa S, Kuroki H, Watanabe M, Beppu T, Tamada M, Nagano O, Saya H, Baba H.
  • Journal Title: Cancer Res Volume: 72 Pages: 3414-23
  • DOI: 10.1158/0008-5472.CAN-12-0299
  • Peer Reviewed
• [Journal Article] Identification of CXCL5 involved in the interaction between cholangiocarcinoma and cancer associated fibroblasts (2012)
  • Author(s): Okabe H, Beppu T, Ueda M, Hayashi H, Ishiko T, Masuda T, Otao R, Hasita H, Mima K, Miyake K, Jono H, Shinriki S, Ando Y, Baba H.
  • Journal Title: Int J Cancer Volume: 131 Pages: 2234-41
  • DOI: 10.1002/ijc.27496
  • Peer Reviewed
• [Journal Article] The role of hepatic stellate cells in the pathogenesis of hepatocellular and cholangiocarcinoma (2011)
  • Author(s): Okabe H, Beppu T, Hayashi H, Ishiko T, Masuda T, Otao R, Horlad H, Baba H.
  • Journal Title: Europ J Clin Med Oncol 2011 Volume: 3: (2)
  • Peer Reviewed
• [Journal Article] Preoperative portal vein embolization (PVE) for patients with hepatocellular carcinoma can improve resectability and may improve disease-free survival (2011)
  • Author(s): Okabe H, Beppu T, Ishiko T, Masuda T, Hayashi H, Otao R, Hasita H, Okabe K, Sugiyama S, Baba H.
  • Journal Title: J Surg Oncol Volume: 104 Pages: 641-6
  • DOI: 10.1002/jso.21928
  • Peer Reviewed
• [Journal Article] Hepatic stellate cells accelerate the malignant behavior of cholangiocarcinoma cells (2011)
  • Author(s): Okabe H, Beppu T, Hayashi H, Ishiko T, Masuda T, Otao R, Hasita H, Jono H, Ueda M, Shinriki S, Ando Y, Baba H.
  • Journal Title: Ann Surg Oncol Volume: 18 Pages: 1175-84
  • DOI: 10.1245/s10434-010-1391-7
  • Peer Reviewed
• [Presentation] Identification of CXCL5/ENA-78 regulating the interaction of cholangiocarcinoma and cancer-associated fibroblasts (2012)
  • Author(s): Okabe H, Beppu T, Ueda M, Hayashi H, Masuda T, Mima K, Nakagawa S, Miyake K, Yokoyama N, Baba Y, Takamori H, Ishiko T, Jono H, Shinriki S, Ando Y, Baba H.
  • Organizer: AACR103th Annual Meeting 2012
  • Place of Presentation: Chicago convention center, IL, USA
  • Year and Date: 20120401-02
• [Presentation] 肝内胆管癌の癌間質相互作用におけるCXCL5の役割 (2012)
  • Author(s): 岡部弘尚、別府透、植田光晴、石河隆敏、近本亮、美馬浩介、中川茂樹、今井克憲、城野博史、高森啓史、安東由喜雄、馬場秀夫
  • Organizer: 第112回日本外科学会定期学術集会
  • Place of Presentation: 千葉(幕張メッセ国際会議場)
  • Year and Date: 2012-04-12
• [Presentation] 質量分析を用いた癌関連線維芽細胞と胆管癌細胞の相互作用を制御する因子CXCLの同定 (2011)
  • Author(s): 岡部弘尚、別府透、植田光晴、石河隆敏、近本亮、増田稔郎、ハスタホスラッド、美馬浩介、城野博史、高森啓史、安東由喜男、馬場秀夫
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋(名古屋国際会議場)
  • Year and Date: 2011-11-03
• [Presentation] Side population cells have some stem-like properties in hepatocellular carcinoma (2011)
  • Author(s): OkabeH, Beppu T, Ishiko T, Chikamoto A, Masuda T, Otao R, Hasita H, Mima K, Takamori H, Baba H.
  • Organizer: AACR102nd Annual Meeting 2011
  • Place of Presentation: Orland convention center, FL, USA.
  • Year and Date: 2011-04-02