title: Role of integrin alpha(v)beta3 in the early phase of liver metastasis: PET and IVM analyses.
abstract: To clarify the function of integrin alpha(v)beta3 in the early stage of liver metastasis, we investigated the interactions of metastatic cells with their target organ under the actual blood flow by using positron emission tomography (PET). The cells used were CHO-K1 cells and their transfectants bearing human integrin alpha(v)beta3 cDNA (alpha(v)beta3-CHO-K1 cells). The liver accumulation of alpha(v)beta3-CHO-K1 cells was significantly higher than that of CHO-K1 cells after injection via the portal vein, whereas no significant difference was observed in the lung accumulation after tail vein injection, suggesting a specific interaction of alpha(v)beta3-CHO-K1 cells with the hepatic sinusoids. Furthermore, to clarify the precise location of each cell in the liver, i.e., to determine whether individual cells were intravascularly localized or had extravasated, we performed intravital fluorescence microscopy (IVM) on the liver by using stable transfectants bearing the green fluorescent protein (GFP) gene, namely, GFP-CHO-K1 and GFP-alpha(v)beta3-CHO-K1 cells. Both types of cells remained in the hepatic blood vessels 1 h after injection via the portal vein. On the other hand, expression of integrin alpha(v)beta3 promoted the cells to reach the extravascular region after 24 h. These results suggest the possibility that the specific accumulation of alpha(v)beta3-CHO-K1 cells in the liver is followed by migration of the cells into the extravascular region. Interestingly, the adhesion of the two types of cells to hepatic sinusoidal endothelial cells in vitro did not correspond to in vivo accumulation of these cells. Therefore, integrin alpha(v)beta3 may function to promote extravasation of integrin alpha(v)beta3-expressing tumor cells in liver through a process possibly mediated by vitronectin produced by this organ.
authors.affiliation: Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Yada, Shizuoka, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Kikkawa
authors.forename: Masako
authors.initials: M
authors.lastname: Kaihou
authors.forename: Natsuko
authors.initials: N
authors.lastname: Horaguchi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Uchida
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Imafuku
authors.forename: Ayano
authors.initials: A
authors.lastname: Takiguchi
authors.forename: Yukako
authors.initials: Y
authors.lastname: Yamazaki
authors.forename: Chieko
authors.initials: C
authors.lastname: Koike
authors.forename: Ryoko
authors.initials: R
authors.lastname: Kuruto
authors.forename: Takeharu
authors.initials: T
authors.lastname: Kakiuchi
authors.forename: Hideo
authors.initials: H
authors.lastname: Tsukada
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Takada
authors.forename: Nariaki
authors.initials: N
authors.lastname: Matsuura
authors.forename: Naoto
authors.initials: N
authors.lastname: Oku
mesh_terms: D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D002478:Cells, Cultured; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology; D019788:Fluorodeoxyglucose F18; D049452:Green Fluorescent Proteins; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000235:genetics / Q000502:physiology*; D007700:Kinetics; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000556:secondary*; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008833:Microcirculation; D008856:Microscopy, Fluorescence; D011652:Pulmonary Circulation; D019275:Radiopharmaceuticals; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014055:Tomography, Emission-Computed; D014162:Transfection
chemical_list: D039302:Integrin alphaVbeta3; D008164:Luminescent Proteins; D019275:Radiopharmaceuticals; D011993:Recombinant Fusion Proteins; D019788:Fluorodeoxyglucose F18; D049452:Green Fluorescent Proteins