title: Decreased roundabout 1 expression promotes development of intrahepatic cholangiocarcinoma.
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.
authors: Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan; Department of Surgery and Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors: Yohei
authors: Y
authors: Mano
authors: Shinichi
authors: S
authors: Aishima
authors: Takasuke
authors: T
authors: Fukuhara
authors: Yuki
authors: Y
authors: Tanaka
authors: Yuichiro
authors: Y
authors: Kubo
authors: Takashi
authors: T
authors: Motomura
authors: Takeo
authors: T
authors: Toshima
authors: Tomohiro
authors: T
authors: Iguchi
authors: Ken
authors: K
authors: Shirabe
authors: Yoshihiko
authors: Y
authors: Maehara
authors: Yoshinao
authors: Y
authors: Oda
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms; D001653:Bile Ducts, Intrahepatic; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D034741:RNA, Small Interfering / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism; D016019:Survival Analysis; D014162:Transfection; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein
keywords: DFS; FBS; GAPDH; ICC; Intrahepatic cholangiocarcinoma; LI; OS; RT-PCR; Robo1; Slit2; disease-free survival; fetal bovine serum; glyceraldehyde-3-phosphate dehydrogenase; intrahepatic cholangiocarcinoma; labeling index; overall survival; reverse transcriptase polymerase chain reaction; roundabout 1