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

BACKGROUND

Adhesion molecules play an integral role in tumor growth, invasion, and metastasis and have been shown to influence the immune response to malignant cells. The interaction of intercellular adhesion molecule-1 (ICAM-1) with lymphocyte function antigen-1 (LFA-1) is important for the adhesion of leukocytes, monocytes and lymphocytes to endothelial cells in vitro and in vivo. In order to explore the role of the ICAM-1/LFA-1 interaction in liver metastases, we utilized homozygous deletionally mutant (gene knockout) mice for ICAM-1 or LFA-1 which had been derived from the C57BL6/J background.

MATERIALS AND METHODS

Wild-type C57BL6/J mice were used as controls. Animals were anesthetized and underwent a 1-cm midline lower abdominal incision. The ileocolic vein was identified and B16 melanoma cells (10(4)) were injected. The incisions were closed with skin clips. Two weeks following surgery, mice were sacrificed and their livers resected for gross and histological analysis.

RESULTS

LFA-1 deficient mice developed 13 times the number of metastases compared to wild-type controls and ICAM-1 deficient mice developed 7 times that 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]: Histologically, multiple areas of inflammatory cells consisting of T-cells and macrophages were noted in wild-type mice. Only sparse inflammatory cells were 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.