[Molecular mechanism in hematogenous metastasis of pancreas carcinoma--possible implication of tumor-derived cytokine in a cell-to-cell interaction of pancreas carcinoma and vascular endothelial cells].
Cellular adhesion between sialyl Lewis a (SLea)-positive pancreas carcinoma and endothelial cells is augmented by exogenous cytokines such as interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha through an upregulated E-selectin expression on endothelial cells. Preincubation of pancreas carcinoma cells with endothelial cells for 4-6 hours at the ratio of 1:10 induced E-selectin expression on endothelial cell surface, and dramatically increased subsequent attachment of SLea-positive pancreas carcinoma with endothelial cells. Paraformaldehyde-fixed PCI cells also induced E-selectin on vascular endothelial cells upon direct contact with endothelial cells. Culture supernatants from all six pancreas carcinoma cell lines contained soluble, E-selectin-inducible factors. Antibodies against SLea and E-selectin but not SLex or ICAM-1 blocked the increased pancreas carcinoma-to-endothelial attachment. These findings suggested that SLea-positive pancreas carcinoma cells produced E-selectin-inducing cytokines, both in the soluble and the membrane bound forms, resulted in augmented attachment to endothelial cells in vitro. The soluble factor lost its activity to induce E-selectin at 70 degrees C, and was different from IL-1-beta or TNF-alpha, because the supernatants contained no measurable IL-1 beta and TNF-alpha. Moreover, pretreatment of the supernatants with specific antibodies to IL-1 beta and TNF-alpha could not neutralize the E-selectin-inducing activity. Instead, all six pancreas carcinoma cell lines produced proteins of IL-1 alpha, and preincubation of the supernatant with specific antibody to IL-1 alpha almost completely removed the E-selectin-inducing activity from the supernatants. The collecting evidence suggests that substances such as IL-1 alpha produced by pancreas carcinoma cells may contribute to hematogenous metastasis of cancers in non-inflamed distant locations.
Kaji
M
M
Second Department of Surgery, Hokkaido University School of Medicine, Sapporo, Japan.
D018395:CA-19-9 Antigen; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000473:pathology*; D005732:Gangliosides / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism / Q000502:physiology*; D009362:Neoplasm Metastasis; D009360:Neoplastic Cells, Circulating; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
D018395:CA-19-9 Antigen; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D005732:Gangliosides; D007375:Interleukin-1; C064564:sialyl Le(a) ganglioside