Importance of E-selectin (ELAM-1) and sialyl Lewis(a) in the adhesion of pancreatic carcinoma cells to activated endothelium.
Adhesion molecules involved in attachment between human pancreatic carcinoma and activated endothelial cells in vitro were investigated. Basal adhesion occurred between 6 pancreatic carcinoma cell lines and unstimulated human umbilical vein endothelial cells (HUVEC), and augmented basal adhesion to activated HUVEC was only seen when pancreatic cancer cells expressed sialyl Lewisa (SLea) and sialyl Lewisx (SLex). Activation of HUVEC with interleukin 1-beta (IL-1 beta) or tumor necrosis factor-alpha (TNF-alpha), but not with interferon-gamma (IFN-gamma), generated the augmentative basal adhesion. Dose dependence and additive effect were observed in augmentation of the basal adhesion induced by IL-1 beta and/or TNF-alpha. Increase in adhesion correlated with up-regulation of the surface E-selectin (or ELAM-1) on HUVEC, and was evident at both 25 degrees C and 4 degrees C. Anti-E-selectin and anti-SLea blocked the augmented attachment, whereas anti-SLex, an antibody against another known ligand for E-selectin, did not. The collective evidence indicates that attachment between pancreas carcinoma cells and activated endothelial cells is regulated by cytokines such as IL-1 beta and TNF-alpha, and is mediated by SLea on pancreas carcinoma and E-selectin on endothelial cells. These molecules may be of significant importance in blood-borne metastasis of pancreatic carcinoma cells to inflamed sites.
Iwai
K
K
Department of Pathology, Hokkaido University School of Medicine, Sapporo, Japan.
Ishikura
H
H
Kaji
M
M
Sugiura
H
H
Ishizu
A
A
Takahashi
C
C
Kato
H
H
Tanabe
T
T
Yoshiki
T
T
D000368:Aged; D000911:Antibodies, Monoclonal; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000502:physiology*; D018395:CA-19-9 Antigen; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology; D019040:E-Selectin; D004730:Endothelium, Vascular / Q000166:cytology / Q000503:physiopathology*; D005260:Female; D005732:Gangliosides / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000503:physiopathology*; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins
D000911:Antibodies, Monoclonal; D015295:Antigens, Tumor-Associated, Carbohydrate; D018395:CA-19-9 Antigen; D015815:Cell Adhesion Molecules; D016207:Cytokines; D019040:E-Selectin; D005732:Gangliosides; C064564:sialyl Le(a) ganglioside