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Phenotypes correlating to metastatic properties of pancreas adenocarcinoma in vivo: The importance of surface sialyl Lewisa antigen

✍ Scribed by Takashi Kishimoto; Hiroshi Ishikura; Chisa Kimura; Toshiyuki Takahashi; Hiroyuki Kato; Takashi Yoshiki


Publisher
John Wiley and Sons
Year
1996
Tongue
French
Weight
553 KB
Volume
69
Category
Article
ISSN
0020-7136

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✦ Synopsis


Metastasis

to the liver often occurs in patients during the natural course of pancreatic cancer. Using carcinoma cell lines established from 9 such patients, we examined phenotypes of cell lines to search for correlations with their potential to metastasize to the liver. Anti-asialo GM I -treated nude mice were used. PCI-43, -55, -24 and -6, in this order, had frequent metastases, while PCI-10, -19, -35, -64, and -66 did not. In vitro doubling time, surface expression of sialyl Lewis' (SLe'), VLA-4/6, LFA-I /3, CEA, E-selectin, VCAM-I, NCAM, Mac-I, HLA-ABC/ DR/DQ, ICAM-I /2, production of interleukin-I a, tumor necrosis factor-a, and matrix metalloproteinase, as well as susceptibility to cytotoxicity by natural killer cells, were all examined. Expression of surface SLe' was significantly associated with metastasis; numbers of metastatic colonies of SLea-positive and -negative cell lines were 21.6 k 33.9 and 6.5 -C 14.3 (p < O.Ol), respectively. Moreover, the intensity of surface SLe" expression of each PCI line correlated with the number of metastatic colonies in the liver. When anti-SLe" monoclonal antibody (MAb) was administered, the development of liver metastasis by PCI-43 cells was significantly repressed, as compared with a control MAb. Although a reverse correlation between surface ICAM-I expression and liver metastasis was noted, the speciesrestricted function of ICAM-I makes interpretation difficult.

Collective evidence indicates that expression of SLea is an important positive mediator in the hematogenous metastasis of pancreas carcinoma.