Decreased roundabout 1 expression promotes development of intrahepatic cholangiocarcinoma

Yohei Mano, Shinichi Aishima, Takasuke Fukuhara, Yuki Tanaka, Yuichiro Kubo, Takashi Motomura, Takeo Toshima, Tomohiro Iguchi, Ken Shirabe, Yoshihiko Maehara, Yoshinao Oda

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Roundabout 1 (Robo1) is a transmembrane receptor of the immunoglobulin family. Slit2 is one of its ligands. The function of Slit2/Robo1 signaling in the development of intrahepatic cholangiocarcinoma (ICC) remains to be elucidated. We examined the immunohistochemical expression of Robo1 and Slit2 and their clinicopathologic implications in 132 cases of ICC. Also, small interfering RNA of Robo1 was transfected into a high-expression ICC cell line, and a Robo1 vector was transfected into a low-Robo1 expression ICC cell line. The effect of Robo1 suppression and overexpression in cell proliferation and migration of cultured ICC cells with Slit2 stimulation was investigated. Immunohistochemical study of ICC in the low-Robo1 expression group showed larger tumors (P =.015), a higher Ki-67 labeling index (P =.021), and low expression of Slit2 (P =.0005). The low-Slit2 expression group frequently showed perineural invasion (P =.036) and lymph node metastases (P =.013). Low Robo1 expression was associated with a poor prognosis (P =.0207). Robo1 suppression in Huh28 cells tended to promote cell proliferation and migration, whereas Robo1 overexpression in RBE cells significantly suppressed cell proliferation and migration. Low Robo1 expression was associated with cell proliferation and migration in ICC and was one of the adverse prognostic factors in patients with these tumors.

Original languageEnglish
Pages (from-to)2419-2426
Number of pages8
JournalHuman Pathology
Volume44
Issue number11
DOIs
Publication statusPublished - Nov 2013

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

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