title: Amigo2-upregulation in Tumour Cells Facilitates Their Attachment to Liver Endothelial Cells Resulting in Liver Metastases.
abstract: Since liver metastasis is the main cause of death in cancer patients, we attempted to identify the driver gene involved. QRsP-11 fibrosarcoma cells were injected into the spleens of syngeneic mice to isolate tumour sub-populations that colonize the liver. Cells from liver metastatic nodules were established and subsequently injected intrasplenically for selection. After 12 cycles, the cell subline LV12 was obtained. Intravenous injection of LV12 cells produced more liver metastases than QRsP-11 cells, whereas the incidence of lung metastases was similar to that of QRsP-11 cells. LV12 cells adhered to liver-derived but not to lung-derived endothelial cells. DNA chip analysis showed that amphoterin-induced gene and open reading frame 2 (Amigo2) was overexpressed in LV12 cells. siRNA-mediated knockdown of Amigo2 expression in LV12 cells attenuated liver endothelial cell adhesion. Ex vivo imaging showed that suppression of Amigo2 in luciferase-expressing LV12 cells reduced attachment/metastasis to liver to the same level as that observed with QRsP-11 cells. Forced expression of Amigo2 in QRsP-11 cells increased liver endothelial cell adhesion and liver metastasis. Additionally, Amigo2 expression in human cancers was higher in liver metastatic lesions than in primary lesions. Thus, Amigo2 regulated tumour cell adhesion to liver endothelial cells and formation of liver metastases.
authors.affiliation: Division of Pathological Biochemistry, Tottori University Faculty of Medicine, Yonago, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kanda
authors.affiliation: Division of Pathological Biochemistry, Tottori University Faculty of Medicine, Yonago, Japan.|Chromosome Engineering Research Center, Tottori University, Yonago, Japan.
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Osaki
authors.affiliation: Division of Pathological Biochemistry, Tottori University Faculty of Medicine, Yonago, Japan.
authors.forename: Kunishige
authors.initials: K
authors.lastname: Onuma
authors.affiliation: Division of Pathological Biochemistry, Tottori University Faculty of Medicine, Yonago, Japan.
authors.forename: Ayana
authors.initials: A
authors.lastname: Sonoda
authors.affiliation: Health Sciences University of Hokkaido, School of Nursing and Social Services, Ishikari-Tobetsu, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Health Sciences University of Hokkaido, School of Nursing and Social Services, Ishikari-Tobetsu, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Hamada
authors.affiliation: Department of Molecular Pathology, The Institute for Molecular Medicine, South Laguna Beach, CA, USA.
authors.forename: Garth L
authors.initials: GL
authors.lastname: Nicolson
authors.affiliation: Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tsukiji, Chuo-ku, Tokyo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ochiya
authors.affiliation: Division of Pathological Biochemistry, Tottori University Faculty of Medicine, Yonago, Japan.|Chromosome Engineering Research Center, Tottori University, Yonago, Japan.
authors.forename: Futoshi
authors.initials: F
authors.lastname: Okada
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor; D002448:Cell Adhesion / Q000235:genetics*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000556:secondary*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology
chemical_list: C476133:Amigo2 protein, mouse; D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins