A fibronectin fragment inhibits tumor growth, angiogenesis, and metastasis.
We have shown previously that a polymeric form of fibronectin is strongly antimetastatic when administered systemically to tumor-bearing mice. The polymeric fibronectin, sFN, is formed in vitro by treating soluble fibronectin with a 76-aa peptide, III1-C, which is derived from the first type III repeat in fibronectin. Here we show that the III1-C peptide and sFN also reduce tumor growth in mice, and that this effect correlates with a low density of blood vessels in the tumors of the treated mice. III1-C also polymerized fibrinogen, and the fibrinogen polymer, sFBG, had antitumor and antiangiogenic effects similar to those of sFN. Mice that had been injected s.c. with three different types of human tumor cells and treated with biweekly i.p. injections of III1-C, sFN, or sFBG over a 5-week period had tumors that were 50-90% smaller than those of control mice. Blood vessel density in the tumors of the treated mice was reduced by 60-80% at the end of the experiment. Xenograft tumors from a human breast carcinoma line (MDA-MB-435) were particularly susceptible to these treatments. Metastasis into the lungs from the primary s.c. tumors also was inhibited in the mice treated with III1-C and the two polymers. The III1-C peptide is an antiangiogenic and antimetastatic agent. Because of its ability to suppress tumor growth, angiogenesis, and metastasis, we have named the III1-C peptide anastellin [from anastello (Greek), inhibit, force a retreat].
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Cancer Research Center, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Ruoslahti
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D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000473:pathology; D001943:Breast Neoplasms / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D005260:Female; D005340:Fibrinogen / Q000494:pharmacology / Q000627:therapeutic use*; D005353:Fibronectins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008545:Melanoma / Q000473:pathology; D008546:Melanoma, Experimental / Q000098:blood supply / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000188:drug therapy*; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D012516:Osteosarcoma / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D019030:Receptors, Vitronectin / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D005353:Fibronectins; D010446:Peptide Fragments; D019030:Receptors, Vitronectin; C423921:anastellin; D005340:Fibrinogen