title: Differential motility stimulation but not growth stimulation or adhesion of metastatic human colorectal carcinoma cells by target organ-derived liver sinusoidal endothelial cells.
abstract: Liver is the most common distant metastatic site for colorectal cancers and when blood-borne colorectal cancer cells reach the liver, they first encounter hepatic capillary and sinusoidal endothelial cells. Thus we studied differences between highly (HT-29LMM) and poorly (HT-29P) liver-metastatic sublines of human colorectal cancer cells by examining the interactions between tumor cells and liver microvessel endothelial cells. Using hepatic sinusoidal endothelial (HSE) and lung microvessel endothelial (MLE) cell-conditioned medium we measured the growth and motility stimulating activities released from these endothelial cells and adhesion of these cancer cells to the endothelial cells. Differences in the ability of HSE-conditioned medium (HSE-CM) or MLE-conditioned medium (MLE-CM) to stimulate HT-29 cell growth were not observed. There was a small but significant increase in the rate of adhesion of highly metastatic HT-29LMM cells to HSE cell monolayers than poorly metastatic HT-29P cells, but there was no difference in adhesion to MLE cell monolayers. HSE-CM stimulated the motility of highly metastatic colorectal cancer cells to a greater extent than the poorly metastatic cells. Motility-stimulating activity for the colorectal cancer cell lines was not detected in MLE-CM. The HSE-CM motility-stimulating activity for human HT-29 cells was not removed using antibodies against hepatocyte growth factor (HGF/SF), complement component C3 or laminin, indicating that it is not related to these known liver-derived motility factors. The results suggest that the ability of highly metastatic HT-29LMM colorectal cancer cells to colonize the liver is related to their ability to respond to liver sinusoidal endothelial cell-derived motility factors and to a lesser degree to adhere to liver sinusoidal endothelial cells.
authors.affiliation: Department of Tumor Biology, University of Texas M.D. Anderson Cancer Center, Houston, USA.
authors.forename: H
authors.initials: H
authors.lastname: Sawada
authors.forename: H
authors.initials: H
authors.lastname: Wakabayashi
authors.forename: A
authors.initials: A
authors.lastname: Nawa
authors.forename: E
authors.initials: E
authors.lastname: Mora
authors.forename: P G
authors.initials: PG
authors.lastname: Cavanaugh
authors.forename: G L
authors.initials: GL
authors.lastname: Nicolson
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000473:pathology*; D017077:Culture Media, Conditioned; D004730:Endothelium, Vascular / Q000166:cytology / Q000473:pathology; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000473:pathology / Q000556:secondary*; D008168:Lung / Q000098:blood supply; D051379:Mice; D014407:Tumor Cells, Cultured
chemical_list: D017077:Culture Media, Conditioned