Stimulation of tumor growth by human soluble intercellular adhesion molecule-1

Because serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) are elevated in cancer and sICAM-1 is angiogenic, we tested the ability of sICAM-1 to promote tumor growth. Our preliminary experiments showed that e xogenous sICAM-1 significantly stimulated the growth of human tumors in viv o. Human fibrosarcoma transfectants, which express ICAM-1, produce ICAM-1 o n the cell surface and release sICAM-1 into the medium without any apparent effect on cell growth in vitro. We found that conditioned medium from sens e ICAM-1 transfectants compared with mock or antisense ICAM-1 transfectants stimulates endothelial cell migration in vitro and neovascularization in t he chick chorioallantoic membrane assay. Tumor cells transfected,vith sense constructs form faster growing tumors than mock- and antisense-transfected cells in both chick embryos and nude mice models. Serum levels of human sI CAM-1 from nude mice bearing sense ICAM-1 transfectants correlate positivel y with tumor weight. Sense ICAM-1 transfectants are more proliferative and induce more blood vessel formation than mock and antisense transfectants in nude mice, Because expression of ICAM-1 does not affect tumor cell growth in vitro the angiogenic activity of sICAM-1 produced by sense ICAM-1 transf ectants may be involved in the stimulation of tumor growth, Therefore, sICA M-1 map perform dual functions that are essential for tumor growth: angioge nesis and escape from immune surveillance.