[Mechanism of blood-borne metastasis in relation to the interaction between pancreatic carcinoma and endothelial cells].
We investigated the interaction between pancreas carcinoma and endothelium, using the originally established human pancreas carcinoma cell lines (PCI), and reported the importance of E-selectin and sialyl Lewis(a) in the adhesion of pancreas carcinoma cells to endothelium activated by inflammatory cytokines. Interestingly, the attachment of PCI to endothelial cells was augmented by preincubation of PCI with endothelial cells through an upregulated E-selectin expression on endothelial cells. Major factor of this activity was IL-1 alpha which was produced by pancreas carcinoma cells. We supposed that tumor-derived IL-1 alpha may contribute to the hematogenous metastasis of cancers in non-inflamed, distant location. In addition to IL-1 alpha, IL-6 also was produced by some, but not all, of PCI cell lines. An endothelial permeability was increased only when endothelial cells were pretreated with the culture supernatant of IL-6-producing cell lines. The activity of supernatant was inhibited by specific antibody reactive for IL-6. Using a liver metastatic model in the nude mouse, we investigated the importance of sialyl Lewis(a) expression and IL-6 production by pancreas carcinoma for progression of metastasis in vivo. Sialyl Lewis(a)-positive cell lines generated more numerous metastatic colonies in the liver than sialyl Lewis(a)-negative cell lines did. PCI lines that produce IL-6 generated significantly less metastases in both number of liver nodules and incidence itself than IL-6-producing PCI did, therefore, surface expression of sialyl Lewis(a) and production of IL-6 appear to be important modulators that regulate hematogenous metastasis of pancreas carcinoma.
Kishimoto
T
T
Department of Pathology, Hokkaido University School of Medicine.
Saito
K
K
Ishikura
H
H
D000818:Animals; D018395:CA-19-9 Antigen; D004730:Endothelium, Vascular / Q000502:physiology*; D005732:Gangliosides / Q000502:physiology; D006801:Humans; D007378:Interleukins / Q000502:physiology; D051379:Mice; D008819:Mice, Nude; D009360:Neoplastic Cells, Circulating; D010190:Pancreatic Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured
D018395:CA-19-9 Antigen; D005732:Gangliosides; D007378:Interleukins; C064564:sialyl Le(a) ganglioside