Inhibition of tumor cell migration by LD22-4, an N-terminal fragment of 24-kDa FGF2, is mediated by Neuropilin 1.

LD22-4, an 86-amino acid fragment of the basic fibroblast growth factor, is an inhibitor of cell migration. LD22-4 inhibits the migration of various tumor cells, endothelial cells, and fibroblasts in vitro and suppresses tumor growth and angiogenesis in vivo. LD22-4 is effective in the presence of multiple growth factors, either alone or in combination, as well as haptotactic factors.

FAK mediates the inhibition of glioma cell migration by truncated 24 kDa FGF-2.

A truncated form of 24kDa FGF-2 consisting of 86 NH(2)-terminal amino acids (ATE+31) inhibits cell migration in vitro and tumor development and angiogenesis in vivo. Focal adhesion kinase (FAK) is phosphorylated on tyrosine and serine sites after cell stimulation by growth factors. This study examined the effect of ATE+31 on FAK phosphorylation in human glioma cells.

Cancer therapy through control of cell migration.

Cell migration plays a pivotal role in a many biological process that are essential for development, repair, and pathogenesis. Thus, inhibition of migration has the potential of limiting or suppressing the development of various diseases. Much of the focus on the therapeutic treatment of cancer has involved compounds that target cell proliferation and subsequent cell death.

NF1 regulatory element functions as a repressor of tissue plasminogen activator expression.

Objective: Analysis of the distribution of endothelial cell tissue plasminogen activator (tPA) in the vasculature of rodents and primates demonstrated that tPA is constitutively expressed predominantly in small artery endothelial cells of brain and lung. The regulatory elements responsible for the highly selective expression of arterial endothelial cell tissue plasminogen activator were sought.

Methods And Results: Transcription factor binding sites were defined by electrophoretic mobility-shift assay (EMSA) analysis using rat lung and brain nuclear extracts and the tPA promoter sequence from -609 to +37 bp.

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.

Inhibition of cell migration and angiogenesis by the amino-terminal fragment of 24kD basic fibroblast growth factor.

The 24-kDa form of basic fibroblast growth factor inhibits the migration of endothelial cells and mammary carcinoma cells while continuing to promote cell proliferation. This molecule consists of the 18-kDa fibroblast growth factor sequence plus an additional 55 amino acids at the amino-terminal end. Antibody neutralization studies suggested that the inhibition of migration is associated with these 55 amino acids, whereas the promotion of proliferation localizes to the 18-kDa domain.