Decreased roundabout 1 expression promotes development of intrahepatic cholangiocarcinoma

作者：Mano Yohei; Aishima Shinichi; Fukuhara Takasuke; Tanaka Yuki; Kubo Yuichiro; Motomura Takashi; Toshima Takeo; Iguchi Tomohiro; Shirabe Ken; Maehara Yoshihiko; Oda Yoshinao^*

来源：Human Pathology, 2013, 44(11): 2419-2426.

DOI：10.1016/j.humpath.2013.03.022

• Intrahepatic cholangiocarcinoma
• Robol
• Slit2

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

• 出版日期2013-11