ENHANCED EXPRESSION OF ICAM-1 IN A MURINE FIBROSARCOMA REDUCES TUMOR-GROWTH RATE

Intercellular adhesion molecule-1 (ICAM-1) plays an essential role in lymphocyte adhesion to endothelium and migration across endothelial ce ll barriers. We undertook this study to determine the growth of a muri ne fibrosarcoma transfected with the ICAM-1 gene. MCA-105 tumor cells were cotransfected with ICAM-1 and the plasmid for neomycin resistance (NeoR). Selected G418-resistant clones were expanded and cell surface ICAM-1 expression was verified using a fluorescence-activated cell so rter. Integration of the ICAM-1 gene and ICAM-1 mRNA expression were v erified by Southern and Northern blot hybridization analysis, respecti vely. C57BL/6 mice were divided into five groups (six animals/group): Control, NeoR only, ICAM-1 (low expressing, Clone 25), ICAM-1 (high ex pressing, Clone 81), and a 1:1 mixture of NeoR:Clone 81; animals recei ved 1 X 10(6) cells on Day 6 and tumor measurements began on Day 7 and were measured in mm(2). At 19 days, tumors from cell lines expressing ICAM-1 were significantly (P < .05) smaller than both the parental ce ll line and tumor-containing NeoR only (364 mm(2) vs 466 mm(2) and 527 mm(2), respectively). This decrease in tumor growth may be a result o f increased lymphocyte migration or increased anti-tumor cytotoxicity by infiltrating lymphocytes. The results from the mixed tumor experime nt suggest a possible paracrine effect by cells expressing ICAM-1. Stu dies are currently under way to investigate the effect of immunotherap y on tumors derived from ICAM-1-cloned transfectants. (C) 1995 Academi c Press, Inc.