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 cell barriers. We undertook this study to determine the growth of a murine 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 sorter. Integration of the ICAM-1 gene and ICAM-1 mRNA expression were verified by Southern and Northern blot hybridization analysis, respectively. C57BL/6 mice were divided into five groups (six animals/group): Control, NeoR only, ICAM-1 (low expressing, Clone 25), ICAM-1 (high expressing, Clone 81), and a 1:1 mixture of NeoR:Clone 81; animals received 1 x 10(6) cells on Day 0 and tumor measurements began on Day 7 and were measured in mm2. At 19 days, tumors from cell lines expressing ICAM-1 were significantly (P < .05) smaller than both the parental cell line and tumor-containing NeoR only (364 mm2 vs 466 mm2 and 527 mm2, respectively). This decrease in tumor growth may be a result of increased lymphocyte migration or increased anti-tumor cytotoxicity by infiltrating lymphocytes. The results from the mixed tumor experiment suggest a possible paracrine effect by cells expressing ICAM-1. Studies are currently under way to investigate the effect of immunotherapy on tumors derived from ICAM-1-cloned transfectants.
Sartor
W M
WM
Tumor Immunology Laboratory, University of Maryland, Baltimore 21201, USA.
Kyprianou
N
N
Fabian
D F
DF
Lefor
A T
AT
D000818:Animals; D005260:Female; D005354:Fibrosarcoma / Q000473:pathology* / Q000628:therapy; D015316:Genetic Therapy; D007167:Immunotherapy; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000502:physiology*; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1