Phenotypic modulation of endothelial cells by transforming growth factor-beta depends upon the composition and organization of the extracellular matrix.
Transforming growth factor beta (TGF-beta) is angiogenic in vivo. In vitro, endothelial cell proliferation is inhibited by TGF-beta. We have correlated this inhibitory effect with an increase in cellular fibronectin synthesis and deposition in a two-dimensional culture system using specific matrix coatings. The inhibitory effect was mimicked by addition of soluble fibronectin to cultures. In contrast, TGF-beta was found to elicit the formation of tube-like structures (mimicking angiogenesis) when microvascular endothelial cells were grown in three-dimensional collagen gels. In this culture system TGF-beta elicited rapid extensive formation of complex, branching, tube-like structures, while cell proliferation was not inhibited. These data confirm and support the hypothesis that TGF-beta is angiogenic and may exert some of its effects through modulation of matrix synthesis and are consistent with the hypothesis that the organization of the extracellular environment influences cellular responses to this "panregulin."
Madri
J A
JA
Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510.
Pratt
B M
BM
Tucker
A M
AM
D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000032:analysis / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D006133:Growth Substances / Q000494:pharmacology*; D007797:Laminin / Q000378:metabolism; D008857:Microscopy, Interference; D010455:Peptides / Q000494:pharmacology*; D010641:Phenotype; D015291:Transforming Growth Factors
D043925:Angiogenesis Inducing Agents; D005353:Fibronectins; D006133:Growth Substances; D007797:Laminin; D010455:Peptides; D015291:Transforming Growth Factors; D003094:Collagen