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Phenotypes correlating to metastatic properties of pancreas adenocarcinoma in vivo: The importance of surface sialyl Lewis a antigen
Author(s) -
Kishimoto Takashi,
Ishikura Hiroshi,
Kimura Chisa,
Takahashi Toshiyuki,
Kato Hiroyuki,
Yoshiki Takashi
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19960822)69:4<290::aid-ijc9>3.0.co;2-s
Subject(s) - metastasis , cancer research , monoclonal antibody , muc1 , adenocarcinoma , in vivo , biology , antigen , medicine , immunology , antibody , cancer , pathology , microbiology and biotechnology
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 GMI‐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 a (SLe a ), VLA‐4/6, LFA‐1/3, CEA, E‐selectin, VCAM‐I, NCAM, Mac‐I, HLA‐ABC/DR/DQ, ICAM‐1/2, production of interleukin‐1α, tumor necrosis factor‐α, and matrix metalloproteinase, as well as susceptibility to cytotoxicity by natural killer cells, were all examined. Expression of surface SLe a was significantly associated with metastasis; numbers of metastatic colonies of SLe a ‐positive and ‐negative cell lines were 21.6 ± 33.9 and 6.5 ± 14.3 ( p < 0.01), respectively. Moreover, the intensity of surface SLe a expression of each PCI line correlated with the number of metastatic colonies in the liver. When anti‐SLe a 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‐1 expression and liver metastasis was noted, the species‐restricted function of ICAM‐1 makes interpretation difficult. Collective evidence indicates that expression of SLe a is an important positive mediator in the hematogenous metastasis of pancreas carcinoma. © 1996 Wiley‐Liss, Inc.