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 exogenous sICAM-1 significantly stimulated the growth of human tumors in vivo. Human fibrosarcoma transfectants, which express ICAM-1, produce ICAM-1 on 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 sense ICAM-1 transfectants compared with mock or antisense ICAM-1 transfectants stimulates endothelial cell migration in vitro and neovascularization in the chick chorioallantoic membrane assay. Tumor cells transfected with sense constructs form faster growing tumors than mock- and antisense-transfected cells in both chick embryos and nude mice models. Serum levels of human sICAM-1 from nude mice bearing sense ICAM-1 transfectants correlate positively 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 transfectants may be involved in the stimulation of tumor growth. Therefore, sICAM-1 may perform dual functions that are essential for tumor growth: angiogenesis and escape from immune surveillance.
Gho
Y S
YS
Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research/NIH, 30 Convent Drive MSC-4370, Bethesda, MD 20892, USA.
Kim
P N
PN
Li
H C
HC
Elkin
M
M
Kleinman
H K
HK
D000230:Adenocarcinoma / Q000098:blood supply / Q000235:genetics / Q000473:pathology; D000482:Allantois / Q000098:blood supply; D000818:Animals; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002642:Chick Embryo; D002823:Chorion / Q000098:blood supply; D017077:Culture Media, Conditioned; D016373:DNA, Antisense / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D005354:Fibrosarcoma / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000502:physiology; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000235:genetics / Q000473:pathology; D012995:Solubility; D014162:Transfection; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; D016373:DNA, Antisense; D018076:DNA, Complementary; D018799:Intercellular Adhesion Molecule-1