Published in Cancer Detection and Prevention 2000; 24(Supplement 1).

Adhesion molecules and tumor progression in a murine T cell lymphoma

T Kaptzan MSc, E Skutelsky PhD, M Michowitz MD, O Itzhaki MSc, S Naffar MSc, J Leibovici DSc

Dept Pathology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel,

The most threatening aspect of neoplastic growths is their capacity to metastasize. A series of AKR lymphoma variants was studied in our laboratory with respect to cellular functions implied in metastatic potential. Adhesion molecules (AMs) could be responsible for some of these functions. AIMS: The aim of the present study was to examine whether the expression of AMs plays a role in AKR lymphoma tumor progression. METHODS: A comparison of the expression of various AMs on AKR lymphoma malignancy variants was assessed by FACS analysis and fluorescence microscopy using anti AM antibodies. The variants in the order of increasing malignancy were: TAU-39, TAU-47, TAU-44, TAU-33, TAU-42 and TAU-46. RESULTS: The expression of L-selectin did not display a clear correlation with malignancy. By contrast, the expression of several integrins was related to tumor aggressiveness. CD11a was significantly higher in the variants of highest malignancy, TAU-42 and TAU-46. The variant of lowest malignancy (TAU-39) displayed a low anti-CD18 binding and the most marked level was observed with the most aggressive variant, TAU-46. The most pronounced difference in fluorescence intensity between the variants of highest and lowest aggressiveness (x27) was observed with VLA-4, indicating that this molecule is of high importance in the tumor progression of AKR lymphoma. Cap formation, related to higher malignancy, was observed in a fraction of cells with anti-CD62L, anti-CD11a and anti-CD18. This may have functional implications, such as increase in migration ability. CONCLUSIONS: In contrast to L-selectin, the three integrins, particularly VLA-4, appear to play a role in the malignant behavior of AKR lymphoma. Information regarding the metastatic phenotype could contribute to the identification of cellular molecules suitable as antimetastatic therapy targets.

KEY WORDS: Adhesion molecules, Tumor Progression, AKR lymphoma.

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Paper presented at the International Symposium on Impact of Biotechnology on Cancer Diagnostic & Prognostic Indicators; Geneva, Switzerland; October 28 - 31, 2000; in the section on metastasis & prevention.