Suppression of tumor growth and angiogenesis in vivo by a truncated form of 24-kd fibroblast growth factor (FGF)-2.
Efforts to treat tumors have routinely depended on disruption of cell proliferation by a variety of methods, many involving stimulation of apoptosis. We have previously shown that a truncated form of 24-kd basic fibroblast growth factor consisting of the amino terminal 86 amino acids inhibits migration of tumor and endothelial cells in vitro. In the present study, this peptide was tested for its ability to suppress angiogenesis and tumor growth using the murine dorsal skin-fold chamber model in vivo. Treatment of MCF-7 breast carcinoma tumor spheroids with this peptide resulted in cessation of the angiogenic response and a significant reduction in tumor size. Blood vessels that did form were poorly developed. In addition to inhibiting angiogenesis, the peptide also inhibited migration of Lewis lung carcinoma cells away from the tumor core before onset of angiogenesis indicating that the peptide-mediated inhibition of migration affects both angiogenesis and tumor growth independently. Despite inhibition of tumor cell migration, the peptide had no effect on neutrophil or eosinophil chemotaxis. This study demonstrates that the truncated form of 24-kd basic fibroblast growth factor is effective in suppressing tumor development in vivo through inhibition of angiogenesis as well as inhibition of tumor cell migration without compromising other homeostatic events.
Levin
Eugene G
EG
Division of Vascular Biology, La Jolla Institute for Molecular Medicine, San Diego, California 92121, USA. glevin@ljimm.org
Sikora
Lyudmila
L
Ding
Lan
L
Rao
Savita P
SP
Sriramarao
P
P
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010446:Peptide Fragments / Q000494:pharmacology*
D020533:Angiogenesis Inhibitors; D010446:Peptide Fragments; D016222:Fibroblast Growth Factor 2