Phenotypes correlating to metastatic properties of pancreas adenocarcinoma in vivo: the importance of surface sialyl Lewis(a) antigen.

Abstract

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-I/3, CEA, E-selectin, VCAM-I, NCAM, Mac-I, HLA-ABC/ DR/DQ, ICAM-I/2, production of interleukin-I alpha, tumor necrosis factor-alpha, and matrix metalloproteinase, as well as susceptibility to cytotoxicity by natural killer cells, were all examined. Expression of surface SLea 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-I expression and liver metastasis was noted, the species-restricted function of ICAM-I makes interpretation difficult. Collective evidence indicates that expression of SLe(a) is an important positive mediator in the hematogenous metastasis of pancreas carcinoma.

• Authors: T Kishimoto, H Ishikura, C Kimura, T Takahashi, H Kato, T Yoshiki
• Journal: International journal of cancer (Int J Cancer) Vol. 69 Issue 4 Pg. 290-4 (Aug 22 1996) ISSN: 0020-7136 [Print] United States
• PMID: 8797870 (Publication Type: Journal Article)

Chemical References

• Antigens, Tumor-Associated, Carbohydrate
• Oligosaccharides
• sialyl-Le(a) oligosaccharide

Topics

• Adenocarcinoma (immunology, pathology, secondary)
• Animals
• Antigens, Tumor-Associated, Carbohydrate (analysis)
• Female
• Humans
• Liver Neoplasms (pathology, secondary)
• Male
• Mice
• Mice, Nude
• Middle Aged
• Neoplasm Transplantation
• Oligosaccharides (analysis)
• Pancreatic Neoplasms (immunology, pathology)
• Phenotype
• Tumor Cells, Cultured