In Vitro Cellular & Developmental Biology

, Volume 23, Issue 5, pp 387–394

Endothelial growth factors and extracellular matrix regulate DNA synthesis through modulation of cell and nuclear expansion

  • Donald E. Ingber
  • Joseph A. Madri
  • Judah Folkman
Rapid Communications in Cell Biology


Studies were carried out to analyze the mechanism by which extracellular matrix (ECM) molecules and soluble growth factors interplay to control capillary endothelial cell growth. Bovine adrenal capillary endothelial cells attached to purified matrix components but spread poorly and exhibited low levels of DNA synthesis in the absence of exogenous growth factors or serum. Addition of cationic, heparin-binding growth factor purified from either human hepatoma cells or normal bovine pituitary (fibroblast growth factor) induced extensive cell spreading and up to eight fold increases in DNA synthetic rates relative to levels observed in cells on similar substrata in the absence of mitogen. However, the extent of this response differed depending upon the type of ECM molecule used for cell attachment (fold increase on type III collagen > gelatin > type IV collagen > fibronectin > type V collagen ⋙ laminin). Computerized morphometry demonstrated that endothelial cell DNA synthetic rates increased in an exponential fashion in direct relation to linear increases in cell and nuclear size (projected areas). Similarly sized cells always displayed the same level of DNA synthesis independent of the type of ECM molecule used for cell attachment or the presence of saturating amounts of growth factor. In all cases, DNA metabolism appeared to be coupled to physical expansion of the cell and nucleus rather than to a specific cell morphology (e.g. polygonal versus bipolar). These findings suggest that ECM may act locally as a “solid state” regulator of angiogenesis through its ability to selectively support or prohibit cell and nuclear extension in response to stimulation by soluble mitogens.

Key words

fibroblast growth factor cell shape nuclear shape signal transduction angiogenesis 


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Copyright information

© Tissue Culture Association, Inc 1987

Authors and Affiliations

  • Donald E. Ingber
    • 1
  • Joseph A. Madri
    • 3
  • Judah Folkman
    • 2
  1. 1.Department of Surgery, The Children's Hospital, Department of PathologyBrigham and Women's HospitalBoston
  2. 2.Department of Anatomy and Cell BiologyHarvard Medical SchoolBoston
  3. 3.Department of PathologyYale University School of MedicineNew Haven
  4. 4.Enders 1021, Surgical Research LaboratoryChildren's HospitalBoston

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