title: Implantation of human colorectal carcinoma cells in the liver studied by in vivo fluorescence videomicroscopy.
abstract: In vivo fluorescence videomicroscopy (IVFM) was used to analyse the behavior of weakly and highly metastatic human colorectal carcinoma (CRC) cells during implantation in the liver. A highly metastatic human CRC cell line, CX-1, and a weakly metastatic line, Clone A, were double-labeled with rhodamine B isothiocyanate-dextran (Rd-Dx) to locate cells and with calcein AM to assess cell metabolic activity in an experimental metastasis model. Double-labeled CRC cells (2.0 x 10(6)) were injected into the spleens of groups of nude mice and the livers observed by IVFM over the next 72 h. CRC cells were implanted within 30 s after injection into either portal venules or the proximal third of hepatic sinusoids. Approximately 0.5% of CRC cells traversed the liver through portal-central venous shunts and implanted in the lung. The number of CX-1 cells in the liver was similar to that of Clone A cells during the first 12 h. However, more CX-1 cells than Clone A cells remained in the liver at 4 h and were in groups of 8-12 cells whereas only a few, single Clone A cells were detected in the liver at 72 h. Not all Clone A cells are committed to die within 4 h of implantation because cells harvested 4 h after hepatic implantation proliferated normally in vitro when removed from the hepatic microenvironment. Since the stress of mechanical deformation during implantation may cause differences in cell survival, CX-1 and Clone A cells were passed through filters with 8 microM pores in vitro at 10-15 cm of water pressure to recreate the trauma of hepatic implantation. Approximately 50% of both CX-1 and Clone A cells were lysed. Furthermore, both CRC lines remained metabolically active when co-cultivated with liver cells for at least 24 h in vitro. Thus, the difference in metastatic potential between the two CRC lines may reside in their response to the combination of mechanical implantation and subsequent growth in the liver parenchyma.
authors.affiliation: Department of Surgery, New England Deaconess Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ishii
authors.forename: T
authors.initials: T
authors.lastname: Mizoi
authors.forename: K
authors.initials: K
authors.lastname: Kawano
authors.forename: O
authors.initials: O
authors.lastname: Cay
authors.forename: P
authors.initials: P
authors.lastname: Thomas
authors.forename: A
authors.initials: A
authors.lastname: Nachman
authors.forename: R
authors.initials: R
authors.lastname: Ford
authors.forename: Y
authors.initials: Y
authors.lastname: Shoji
authors.forename: J B
authors.initials: JB
authors.lastname: Kruskal
authors.forename: G
authors.initials: G
authors.lastname: Steele
authors.forename: J M
authors.initials: JM
authors.lastname: Jessup
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000473:pathology*; D002448:Cell Adhesion; D002470:Cell Survival; D002999:Clone Cells; D015179:Colorectal Neoplasms / Q000473:pathology*; D005456:Fluorescent Dyes; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D013314:Stress, Mechanical; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014741:Video Recording
chemical_list: D005456:Fluorescent Dyes