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

• 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
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: CAF（癌関連線維芽細胞） / 胆管癌 / 肝星細胞 / myofibroblast / 組織消化 / 癌関連線維芽細胞 / 肝内胆管癌 / 線維芽細胞

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) Issue: 3 Pages: 964-976
  • 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 Issue: 5 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) Issue: 5 Pages: 1003-11
  • DOI: 10.1093/carcin/bgt402
  • Peer Reviewed / Open Access
• [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 and Baba H
  • Journal Title: Br J Cancer Volume: 印刷中 Issue: 4 Pages: 958-66
  • DOI: 10.1038/bjc.2013.759
  • 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: In press
  • Peer Reviewed
• [Journal Article] Epigenetic therapy with the histone methyltransferase EZH2 inhibitor 3-deazaneplanocin A inhibits the growth of cholangiocarcinoma cells. (2014)
  • Author(s): Nakagawa S, Sakamoto Y, Okabe H, Hayashi H, Hashimoto D, Yokoyama N, Tokunaga R, Sakamoto K, Kuroki H, Mima K, Beppu T, Baba H.
  • Journal Title: Oncology Report Volume: 31 Issue: 2 Pages: 983-8
  • DOI: 10.3892/or.2013.2922
  • 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) Issue: 4 Pages: 614-21
  • 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) Issue: 8 Pages: 1447-51
  • DOI: 10.1007/s11605-013-2237-y
  • Peer Reviewed
• [Journal Article] Mima K, Hayashi H, Kuroki H, NakagawaS, Okabe H, Chikamoto A, Watanabe M,Beppu T, Baba H (2013)
  • Author(s): Mima K, Hayashi H, Kuroki H, NakagawaS, Okabe H, Chikamoto A, Watanabe M,Beppu T, Baba H
  • Journal Title: Oncology Lett Volume: 5 Issue: 1 Pages: 149-154
  • DOI: 10.3892/ol.2012.954
  • Peer Reviewed
• [Journal Article] High CD44s expression is associatedwith the EMT expression profile andintrahepatic dissemination ofhepatocellular carcinoma after localablation therapy. (2013)
  • Author(s): Mima K, Hayashi H,Imai K, Kuroki H,Shigaki N, Nakagawa S, Okabe H,Chikamoto A, Watanabe M, Beppu T, BabaH
  • Journal Title: J Hepatobiliary Pancreatic Surg Volume: 20 Issue: 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] CD44v6 expression is related to mesenchymal phenotype and poor prognosis in patients with colorectal cancer. (2012)
  • Author(s): Saito S, Miyamoto Y, et al.
  • Journal Title: Oncol Rep. Volume: 29 Issue: 4 Pages: 1570-8
  • DOI: 10.3892/or.2013.2273
  • Peer Reviewed
• [Journal Article] Kinoshita H, Okabe H, Beppu T,Chikamoto A, Hayashi H, Imai K, MimaK, Nakagawa S, Ishimoto T, Miyake K,Yokoyama N, Ishiko T, Baba (2012)
  • Author(s): Kinoshita H, Okabe H, Beppu T,Chikamoto A, Hayashi H, Imai K, MimaK, Nakagawa S, Ishimoto T, Miyake K,Yokoyama N, Ishiko T, Baba
  • Journal Title: Oncol Rep Volume: 29 Issue: 2 Pages: 685-9
  • DOI: 10.3892/or.2012.2162
  • Peer Reviewed
• [Journal Article] Upregulation of ERCC1 and DPDexpressions after oxaliplatin-basedfirst-line chemotherapy formetastatic 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 Issue: 12 Pages: 1950-5
  • DOI: 10.1038/bjc.2012.502
  • Peer Reviewed
• [Journal Article] External biliary drainage and liver regeneration after major hepatectomy. (2012)
  • Author(s): 太田尾 龍、岡部 弘尚、他
  • Journal Title: British Journal of Surgery Volume: 99 Issue: 11 Pages: 1569-1574
  • DOI: 10.1002/bjs.8906
  • Peer Reviewed
• [Journal Article] CD44s regulates the TGF-β-mediatedmesenchymal phenotype and isassociated with poor prognosis inpatients with hepatocellularcarcinoma. (2012)
  • Author(s): Mima K, Okabe H, Ishimoto T, HayashiH, Nakagawwa S, Kuroki H, Watanabe M
  • Journal Title: Cancer Res Volume: 72 Issue: 13 Pages: 3414-23
  • DOI: 10.1158/0008-5472.can-12-0299
  • Peer Reviewed
• [Journal Article] Identification of CXCL5/ENA-78 as afactor involved in the interactionbetween cholangiocarcinoma cells andcancer-associated fibroblasts. (2012)
  • Author(s): Okabe H, Beppu T, Ueda M, Hayashi H,Ishiko T, Masuda T, Otao R, Horlad H,Mima K, Miyake K, Iwatsuki M, Baba Y,Takamori H, Jono H, Shinriki S, AndoY, Baba H
  • Journal Title: Int J Cancer 131 Volume: in press Issue: 10 Pages: 2234-41
  • DOI: 10.1002/ijc.27496
  • Peer Reviewed
• [Journal Article] Combined measurements of serum bileacid level and splenic volume may beuseful to noninvasively assess theportal venous pressure. (2012)
  • Author(s): Hayashi H, Beppu T, Kuroki H, NakagawaS, Mima K, Okabe H, Nitta H, Imai K,Chikamoto A, Baba H
  • Journal Title: J Gastroenterol Volume: 47 Issue: 12 Pages: 1336-1341
  • DOI: 10.1007/s00535-012-0599-7
  • Peer Reviewed
• [Journal Article] Identification of CXCL5/ENA-78 as a factor involved in the interaction between cholangiocarcinoma cells and cancer-associated fibroblasts (2012)
  • Author(s): Hirohisa Okabe
  • Journal Title: International Journal of Cancer Volume: in press
  • 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 veinembolization (PVE) for patients withhepatocellular carcinoma can improveresectability and may improvedisease-free survival (2011)
  • Author(s): Okabe H, Beppu T, Ishiko T, Masuda T,Hasyashi H, Otao R, Hasta H, Okabe K,Sugiyama S, Baba H
  • Journal Title: J Surg Oncol Volume: 104 Issue: 6 Pages: 641-6
  • DOI: 10.1002/jso.21928
  • Peer Reviewed
• [Journal Article] Hepatic stellate cells acceleratethe malignant behavior ofcholangiocarcinoma. (2011)
  • Author(s): DOI:10.5772/51793kabe H, Beppu T, Hayashi H, Ishiko T,Masuda T, Otao R, Shinriki S, HorladH, Jono H, Ueda M, Ando Y, Baba H
  • Journal Title: Ann Surg Oncol Volume: 18 Issue: 4 Pages: 1175-84
  • DOI: 10.1245/s10434-010-1391-7
  • Peer Reviewed
• [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] 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
• [Presentation] Identification of CXCL5/ENA-78 regulating the interaction of cholangiocarcinoma and cancer-associated fibroblasts (2012)
  • Author(s): 岡部 弘尚、他
  • Organizer: American Association for Cancer Research
  • Place of Presentation: Chicago, USA
• [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
  • Organizer: 日本外科学会
  • Place of Presentation: 幕張メッセ
• [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