A polymeric form of fibronectin has antimetastatic effects against multiple tumor types.
Metastasis accounts for most deaths in cancer patients. Tumor cell adhesion to the extracellular matrix through integrins is thought to be a critical step in metastasis and a potential target for therapeutic intervention. We show here that treatment of human osteosarcoma, melanoma and carcinoma cells with a polymeric form of fibronectin (sFN), before inoculation into nude mice, prevented tumor formation. Intraperitoneally administered sFN significantly reduced lung colonization from intravenously injected tumor cells (experimental metastasis) and from subcutaneous tumors in nude mice (spontaneous metastasis). Treatment with sFN blocked cell spreading and migration in vitro suggesting a possible mechanism for the antimetastatic effect.
La Jolla Cancer Research Center, Burnham Institute, California 92037, USA.
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R
Pasqualini
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Bourdoulous
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Koivunen
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VL
Woods
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E
Ruoslahti
D000818:Animals; D015197:Carcinogenicity Tests; D005260:Female; D005353:Fibronectins / Q000378:metabolism / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D007274:Injections, Intraperitoneal; D016023:Integrins / Q000378:metabolism; D008545:Melanoma / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009374:Neoplasms, Experimental / Q000517:prevention & control*; D012516:Osteosarcoma / Q000473:pathology / Q000517:prevention & control*; D014407:Tumor Cells, Cultured
D005353:Fibronectins; D016023:Integrins