Liver metastases are enhanced in homozygous deletionally mutant ICAM-1 or LFA-1 mice

Background. Adhesion molecules play an integral role in tumor growth, invas ion, and metastasis and have been shown to influence the immune response to malignant cells, The interaction of intercellular adhesion molecule-1 (ICA M-1) with lymphocyte function antigen-1 (LFA-1) is important for the adhesi on of leukocytes, monocytes and lymphocytes to endothelial cells in vitro a nd in vivo. In order to explore the role of the ICAM-1/LFA-1 interaction in liver metastases, we utilized homozygous deletionally mutant (gene knockou t) mice for ICAM-1 or LFA-1 which had been derived from the C57BL6/J backgr ound. Materials and methods. Wild-type C57BL6/J mice were used as controls. Anima ls were anesthetized and underwent a 1-cm midline lower abdominal incision. The ileocolic vein was identified and B16 melanoma cells (10(4)) were inje cted. The incisions were closed with skin clips. Two weeks following surger y, mice were sacrificed and their livers resected for gross and histologica l analysis. Results. LFA-1 deficient mice developed 13 times the number of metastases c ompared to wild-type controls and ICAM-1 deficient mice developed 7 times t hat number [13.5 (n = 17) vs 1.0 (n = 19) and 36 (n = 10) vs 5.0 (n = 16), P values of 0.0003 and 0.0002 by Wilcoxon Rank Sum Test, respectively]. His tologically, multiple areas of inflammatory cells consisting of T-cells and macrophages were noted in wild-type mice. Only sparse inflammatory cells w ere noted surrounding the metastases in the null mice. Conclusions. Liver metastases of the B16 melanoma are markedly enhanced in ICAM-1 null and LFA-1 null mice. The ICAM-1/LFA-1 interaction is crucial to the immune response to liver metastases. (C) 1998 Academic Press.