Endothelial growth factors and extracellular matrix regulate DNA synthesis through modulation of cell and nuclear expansion
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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.
- Bernfield, M. R.; Banerjee, S. D. The basal lamina in epithelial-mesenchymal interactions. Kefalides, N. ed. Biology and Chemistry of Basement Membranes. New York: Academic Press; 1978; 137–148.
- Bissell, M. J.; Hall, H. G.; Parry, G. How does the extracellular matrix direct gene expression? J. Theor. Biol. 99:31–68; 1982. CrossRef
- Bohlen, P.; Baird, A.; Esch, F.; Ling, N.; Gospodarowicz, D. Isolation and partial molecular characterization of pituitary fibroblast growth factor. Proc. Natl. Acad. Sci. USA 81:5364–5368; 1984. CrossRef
- Cervera, M.; Dreyfuss, G.; Penman, S. Messenger RNA is translated when associated with the cytoskeletal framework in normal and VSV-infected HeLa cells. Cell 23:113–120; 1981. CrossRef
- Coffey, D. S.; Barback, E. R.; Heston, W. D. W. The regulation of nuclear DNA template restrictions by acidic polymers. Weber, G. ed. Avances in Enzyme Regulation. New York: Pergamon Press; 12:219–266, 1974.
- Connolly, D. T.; Knight, M. B.; Harakas, N. K.; Wittwer, A. J.; Feder, J. Determination of the number of endothelial cells in culture using an acid phosphatase assay. Anal. Biochem. 152:136–140; 1986. CrossRef
- Esch, F.; Baird, A.; Ling, N.; Ueno, N.; Hill, F.; Denoroy, L.; Klepper, R.; Gospodarowicz, D.; Bohlen, P.; Guillemin, R. Primary structure of bovine pituitary basic fibroblast growth factor (FGF) and comparison with the amino-terminal sequence of brain acidic FGF. Proc. Natl. Acad. Sci. USA 82:6507–6511; 1985. CrossRef
- Evans, R. B.; Morhenn, V.; Jones, A. L.; Tomkins, G. M. Concomittant effects of insulin on surface membrane conformation and polysome profiles of serum-starved BALB/C 3T3 fibroblasts. J. Cell Biol. 61:95–106; 1974. CrossRef
- Fey, E. G.; Wan, K. M.; Penman, S. Epithelial cytoskeletal framework and nuclear matrix-intermediate filament scaffold: three dimensional organization and protein composition. J. Cell Biol. 98:1973–1984; 1984. CrossRef
- Folkman, J.; Moscona, A. Role of cell shape in growth control. Nature 273:345–349; 1978. CrossRef
- Folkman, J.; Haudenschild, C. C.; Zetter, B. R. Long term culture of capillary endothelial cells. Proc. Natl. Acad. Sci. USA 76:5217–5221; 1979. CrossRef
- Folkman, J. Angiogenesis: initiation and control. Ann. NY Acad. Sci. 401:212–227; 1982. CrossRef
- Form, D. M.; Pratt, B. M.; Madri, J. A. Endothelial cell proliferation during angiogenesis: in vitro modulation by basement membrane components. Lab. Invest. 55:521–528; 1986.
- Gitlin, J. D.; D'Amore, P. A. Culture of retinal capillary cells using selective growth media. Microvasc. Res. 26:74–80; 1983. CrossRef
- Gospodarowicz, D.; Greenburg, G.; Birdwell, C. R. Determination of cellular shape by the extracellular matrix and its correlation with the control of cellular growth. Canc. Res. 38:4155–4171; 1978.
- Gospodarowicz, D. The control of mammalian cell proliferation by growth factors, basement lamina, and lipoproteins. J. Invest. Derm. 81:40s-50s; 1983. CrossRef
- Grobstein, C. Mechanisms of organogenetic tissue interaction. Natl. Cancer Inst. Monogr. 26:279–299; 1967.
- Harris, A. K.; Wild, P.; Stopak, D. Silicone rubber substrata: a new wrinkle in the study of cell locomotion. Science 208:177–179; 1980. CrossRef
- Hill, T. L.; Kirschner, M. W. Bioenergetics and kinetics of microtubule and actin filament assembly-disassembly. Int. Rev. Cytol. 78:1–125; 1982. CrossRef
- Ingber, D. E.; Jamieson, J. D. Cells as tensegrity structures: architectural regulation of histodifferentiation by physical forces transduced over basement membrane. Andersson, L. C.; Gahmberg, C. G.; Ekblom, P. eds. Gene Expression During Normal and Malignant Differentiation. Orlando: Academic Press; 1985:13–32.
- Ingber, D. E.; Madri, J. A.; Jamieson, J. D. Role of basal lamina in the neoplastic disorganization of tissue architecture. Proc. Natl. Acad. Sci. USA 78:3901–3905; 1981. CrossRef
- Ingber, D. E.; Madri, J. A.; Jamieson, J. D. Basement membrane as a spatial organizer of polarized epithelia: exogenous basement membrane reorients pancreatic epithelial tumor cells in vitro. Am. J. Pathol. 122:129–139; 1986.
- Ingber, D. E.; Madri, J. A.; Folkman, J. A possible mechanism for inhibition of angiogenesis by angiostatic steroids: induction of basement membrane dissolution. Endocrinol. 119:1768–1775; 1986. CrossRef
- Iwig, M.; Glaesser, D.; Bethge, M. Cell shape-mediated growth control of lens epithelial cells grown in culture. Exp. Cell Res. 131:47–55; 1981. CrossRef
- Jones, J. C.; Goldman, A. E.; Yang, H. Y.; Goldman, R. D. The organizational fate of intermediate filament networks in two epithelial cell types during mitosis. J. Cell Biol. 100:93–102; 1985. CrossRef
- Joshi, H. C.; Chu, D.; Buxbaum, R. E.; Heidemann, S. R. Tension and compression in the cytoskeleton of PC 12 neurites. J. Cell Biol. 101:697–705; 1985. CrossRef
- Klagsbrun, M.; Smith, S. Purification of a cartilage-derived growth factor. J. Biol. Chem. 255:10859–10866; 1980.
- Klagsbrun, M.; Sullivan, R.; D'Amore, P.; Butterfield, C.; Folkman, J. Stimulation of capillary endothelial cell proliferation by tumor-derived growth factors. J. Cell Biol. 95:201a;1982.
- Klagsbrun, M.; Sasse, J.; Sullivan, R.; Smith, J. A. Human tumor cells synthesize an endothelial cell growth factor that is structurally related to basic fibroblast growth factor. Proc. Natl. Acad. Sci. USA 83:2448–2452; 1986. CrossRef
- Kram, R.; Tomkins, G. M. Pleiotypic control by cyclic AMP: Interactions with cGMP and possible role of microtubules. Proc. Natl. Acad. Sci. USA 70:1659–1663; 1979. CrossRef
- Lawrence, T. S.; Ginzberg, R. D.; Gilula, N. B.; Beers, W. H. Hormonally induced cell shape changes in cultured rat ovarian granulosa cells. J. Cell Biol. 80:21–36; 1979. CrossRef
- Lobb, R.; Sasse, J.; Sullivan, R.; Shing, Y.; D'Amore, P.; Jacobs, J.; Klagsbrun, M. Purification and characterization of heparin-binding endothelial cell growth factors. J. Biol. Chem. 261:1924–1928; 1986.
- Madri, J. A.; Furthmayr, H. The collagenous components of the subendothelium: correlation of structure and function. Lab. Invest. 43:303–315; 1980.
- Madri, J. A.; Stenn, K. S. Aortic endothelial cell migration. I. Matrix requirements and composition. Am. J. Pathol. 106:180–188; 1982.
- Madri, J. A. The preparation of Type V collagen. Furthmayr, H. ed. The Immunocytochemistry of the Extracellular Matrix. Boca Raton: CRC Press; 1:75–90; 1982.
- Madri, J. A.; Williams, S. K. Capillary endothelial cell cultures: phenotypic modulation by matrix components. J. Cell Biol. 97:153–165; 1983. CrossRef
- Neufeld, G.; Gospodarowicz, D. The identification and partial characterization of the fibroblast growth factor receptor of baby hamster kidney cells. J. Biol. Chem. 260:13860–13868; 1985.
- Pardoll, D. M.; Vogelstein, B.; Coffey, D. S. A fixed site of DNA replication in eucaryotic cells. Cell 19:527–536; 1980. CrossRef
- Salomon, D. S.; Liotta, L. A.; Kidwell, W. R. Differential response to growth factor by rat mammary epithelium plated on different collagen substrata in serum-free medium. Proc. Natl. Acad. Sci. USA 78:382–386; 1981. CrossRef
- Schreiber, A. B.; Libermann, T. A.; Lax, I.; Yarden, Y.; Schlessinger, J. Biological role of epidermal growth factor receptor clustering: investigation with monoclonal anti-receptor antibodies. J. Biol. Chem. 258:846–853; 1982.
- Schweigerer, L.; Neufeld, G.; Friedman, J.; Abraham, J. A.; Fiddes, J. C.; Gospodarowicz, D. Capillary endothelial cells express basic fibroblast growth factor, a mitogen that promotes their own growth. Nature 325:257–259; 1987. CrossRef
- Shing, Y.; Folkman, J.; Sullivan, R.; Butterfield, C.; Murray, J.; Klagsbrun, M. Heparin affinity: purification of a tumor-derived capillary endothelial cell growth factor. Science 223:1296–1299; 1984. CrossRef
- Stenn, K. S.; Madri, J. A.; Roll, F. J. Migrating epidermis produces AB2 collagen and requires continual collagen synthesis for movement. Nature 277:229–232; 1979. CrossRef
- Wicha, M. S.; Liotta, L. A.; Garbisa, S.; Kidwell, W. R. Basement membrane collagen requirements for attachment and growth of mammary epithelium. Exp. Cell Res. 124:181–190; 1979. CrossRef
- Wicha, M. S.; Liotta, L. A.; Vonderhaar, B. K.; Kidwell, W. R. Effects of inhibition of basement membrane collagen deposition on rat mammary gland development. Dev. Biol. 80:253–263; 1980. CrossRef
- Wolosewick, J. J.; Porter, K. R. Microtrabecular lattice of the cytoplasmic ground substance. J. Cell Biology 82:114–139; 1979. CrossRef
- Yahara, I.; Edelman, G. M. Modulation of lymphocyte receptor mobility by locally bound concanavalin A. Proc. Natl. Acad. Sci. USA 72:1579–1583; 1975. CrossRef
- Endothelial growth factors and extracellular matrix regulate DNA synthesis through modulation of cell and nuclear expansion
In Vitro Cellular & Developmental Biology
Volume 23, Issue 5 , pp 387-394
- Cover Date
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- fibroblast growth factor
- cell shape
- nuclear shape
- signal transduction
- Industry Sectors
- Author Affiliations
- 1. Department of Surgery, The Children's Hospital, Department of Pathology, Brigham and Women's Hospital, 02115, Boston, Massachusettes
- 3. Department of Pathology, Yale University School of Medicine, 06510, New Haven, Connecticut
- 4. Department of Anatomy and Cell Biology, Harvard Medical School, 02115, Boston, Massachusettes