Significance of the structure of cancer stroma in intra-hepaticcholangiocellular carcinoma

2012 Fiscal Year Final Research Report

• Project/Area Number: 23790823
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Kurume University
• Principal Investigator: KUWAHARA Reiichiro 久留米大学, 医学部, 助教 (30389275)
• Project Period (FY): 2011 – 2012
• Keywords: 肝臓病学

Research Abstract

Intra-hepatic cholangiocellular carcinoma (IHCCC) is adenocarcinoma,caracterized by the enrichment of fibrous stroma. Fibroblasts, recognized as cancer-associated fibroblasts (CAF), are surrounding tha solid tumor and promote invation and metastasis of the cancer cells. The putative origins of CAF are (1) fibroblast in the organ, (2) bone marrow, (3) epithelial-mesenchymal transition of cancer cells. No investigation for the origin of CAF in IHCCC is reported to date. By the transfection method with the retroviral vector pRetroQ-AcGFPN (Clontech), the human IHCCC cell line (GFP/KMC-1) which expresses GFP protein constantly was established. The clone was characterized by immunohistochemistry and western blotting of epithelial and mesenchymal markers and selected for xenografts in BALB c/nude mice. The optimum injection sites for the tumor formation were subcutaneous tissue and abdominal cavity. Tumor tissue were taken approximately day 20 following xenograft of GFP/KMC -1. The analyssof immunohistochemistry and FISH are underway to investigate the origin of CAF in IHCCC. In the investigation for the expression of EMT genes in the human resected tumors, we found that Snail and Twist genes are expressed at the invasive front of tumors surroundingby CAF.

Research Products

• [Journal Article] Risk factors for hepatocellular carcinoma in Japanese patients with autoimmune hepatitis type 1. Hino-Arinaga T, Ide T (2012)
  • Author(s): Kuromatsu R, Miyajima I, Ogata K, Kuwahara R, Hisamochi A, Torimura T, Sata M; Autoimmune Hepatitis Study Group.
  • Journal Title: J Gastroenterol Volume: 47 (5) Pages: 569-576
  • Peer Reviewed
• [Journal Article] Epithelial cell adhesion molecule (EpCAM) marks hepatocytes newly derived from stem/progenitor cells in humans. (2011)
  • Author(s): Yoon SM, Gerasimidou D, Kuwahara R, Hytiroglou P, Yoo JE, Park YN
  • Journal Title: Theise ND. Hepatology Volume: 53 (3) Pages: 964-973
  • Peer Reviewed
• [Journal Article] Metronomic S-1 chemotherapy and vandetanib: an efficacious nontoxic treatment for hepatocellular carcinoma. (2011)
  • Author(s): Iwamoto H, Torimura T, Nakamura T, Hashimoto O, Inoue K, Kurogi J, Niizeki T, Kuwahara R, Abe M, Koga H, Yano H, Kerbel RS, Ueno T
  • Journal Title: Sata M. Neoplasia Volume: 13 (3) Pages: 187-197
  • Peer Reviewed