Stanniocalcin 1 Is an Autocrine Modulator of Endothelial Angiogenic Responses to Hepatocyte Growth Factor

Autor: Nicholas F. Paoni, Ralph H. Schwall, Jo-Anne Hongo, Gladys Ingle, Constance H. Zlot, Suya Yang, Zhong Sheng, Mary E. Gerritsen, Franklin Peale, Fay Wang
Rok vydání: 2003
Předmět:
Male
Vascular Endothelial Growth Factor A
Umbilical Veins
Time Factors
Angiogenesis
medicine.medical_treatment
Basic fibroblast growth factor
Biochemistry
Mesoderm
Mice
chemistry.chemical_compound
Cell Movement
Phosphorylation
Cells
Cultured
Hepatocyte Growth Factor
Antibodies
Monoclonal
Protein-Tyrosine Kinases
Proto-Oncogene Proteins c-met
Vascular endothelial growth factor
Vascular endothelial growth factor B
Drug Combinations
Vascular endothelial growth factor A
Vascular endothelial growth factor C
Fibroblast Growth Factor 2
Proteoglycans
Hepatocyte growth factor
Collagen
Cell Division
medicine.drug
Genetic Vectors
Neovascularization
Physiologic
Biology
medicine
Animals
Humans
Endothelium
RNA
Messenger
Molecular Biology
Glycoproteins
Wound Healing
Dose-Response Relationship
Drug
Growth factor
Cell Biology
Enzyme Activation
Mice
Inbred C57BL
chemistry
Focal Adhesion Kinase 1
Focal Adhesion Protein-Tyrosine Kinases
Cancer research
Endothelium
Vascular
Laminin
Zdroj: Journal of Biological Chemistry. 278:47654-47659
ISSN: 0021-9258
DOI: 10.1074/jbc.m301353200
Popis: Stanniocalcin 1 (STC1) is a secreted glycoprotein originally described as a hormone involved in calcium and phosphate homeostasis in bony fishes. We recently identified the mammalian homolog of this molecule to be highly up-regulated in an in vitro model of angiogenesis, as well as focally and intensely expressed at sites of pathological angiogenesis (e.g. tumor vasculature). In the present study, we report that STC1 is a selective modulator of hepatocyte growth factor (HGF)-induced endothelial migration and morphogenesis, but not proliferation. STC1 did not inhibit proliferative or migratory responses to vascular endothelial growth factor or basic fibroblast growth factor. The mechanism of STC1 inhibitory effects on HGF-induced endothelial migration seem to occur secondary to receptor activation because STC1 did not inhibit HGF-induced c-met receptor phosphorylation, but did block HGF-induced focal adhesion kinase activation. In the mouse femoral artery ligation model of angiogenesis, STC1 expression closely paralleled that of the endothelial marker CD31, and the peak level of STC1 expression occurred after an increase in HGF expression. We propose that STC1 may play a selective modulatory role in angiogenesis, possibly serving as a "stop signal" or stabilizing factor contributing to the maturation of newly formed blood vessels. HGF is a mesenchyme-derived pleiotropic factor with mitogenic, motogenic, and morphogenic activities on a number of different cell types. HGF effects are mediated through a specific tyrosine kinase, c-met, and aberrant HGF and c-met expression are frequently observed in a variety of tumors. Recent studies have shown HGF to be a potent growth factor implicated in wound healing, tissue regeneration, and angiogenesis.
Databáze: OpenAIRE
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