PROTECTION FROM LYMPHOMA CELL METASTASIS IN ICAM-1 MUTANT MICE - A POSTHOMING EVENT

It has been hypothesized that the intercellular adhesion receptors use d by normal cells could also be operative in the spreading of circulat ing malignant cells to target organs. In the present work, we show tha t genetic ablation of the ICAM-1 gene confers resistance to T cell lym phoma metastasis, Following i.v. inoculation of LFA-1-expressing malig nant T lymphoma cells, we found that ICAM-1-deficient mice were almost completely resistant to the development of lymphoid malignancy compar ed with wild-type control mice that developed lymphoid tumors in the k idneys, spleen, and liver, Histologic examinations confirmed that ICAM -1-deficient mice, in contrast to wild-type mice, had no evidence of l ymphoid infiltration in these organs. The effect of ICAM-1 on T cell l ymphoma metastasis was observed in two distinct strains of ICAM-1-defi cient animals. Nonetheless, lymphoma cells migrated with the same effi ciency to target organs in both normal and ICAM-1-deficient mice, indi cating not only that ICAM-1 expression by the host is essential in lym phoma metastasis, but also that this is so at stages subsequent to hom ing and extravasation into target organs. These results point to posth oming events as a focus of future investigation on the control of meta stasis mediated by ICAM-1.