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The body as a manufacturer of endostatin

Nature Biotechnology volume 17, pages 336–337 (1999)Cite this article

The genome revolution has opened the door not only to understanding biologic processes in health and disease, but also to the potential of using newly characterized genes and their products as drugs to prevent or treat disease. Such is the hope for angiostatin and endostatin, two proteins identified by Judah Folkman and colleagues1,2 as naturally occurring antiangiogenic molecules (i.e., mediators that normally function to suppress the formation of new blood vessels). Considerable controversy has surrounded Folkman's work in the previous year, much of which appears to have centered on the difficulty of obtaining purified protein that remains biologically active. In this issue, Paul Blezinger et al.3 present one way of getting around this problem. They have used gene therapy to deliver the endostatin gene to mouse muscle, where it is expressed in situ and secreted into the blood, resulting in suppression of the growth of murine tumors.

Both angiostatin and endostatin were originally identified as products of tumors. Based on the observation that tumor metastases sometimes grow rapidly following removal of a primary tumor, the Folkman laboratory hypothesized that primary tumors produce molecules that suppress metastatic growth, and discovered angiostatin and endostatin by screening animals with experimental tumors for antitumor mediators. Angiostatin, a 38 kDa single-chain protein, is an internal fragment of plasminogen1. Endostatin, a 20 kDa protein, represents the C-terminal fragment of collagen XVIII2.

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Figure 1: Antiangiogenesis gene therapy using endostatin has been surrounded by considerable controversy in the headlines of US national newspapers.

References

  1. O'Reilly, M.S. et al. Cell 79, 315–328 (1994).

    Article  CAS  Google Scholar 

  2. O'Reilly, M.S. et al. Cell 88, 277–285 (1997).

    Article  CAS  Google Scholar 

  3. Blezinger, P. et al. Nat. Biotechnol. 17, 343– 348 (1999).

    Article  CAS  Google Scholar 

  4. Augustin, H.G. Trends Pharmacol. Sci. 19, 216–22 (1998).

    Article  CAS  Google Scholar 

  5. Kong, H-L. & Crystal, R.G. J. Natl. Cancer Inst. 90, 273–286 (1998).

    Article  CAS  Google Scholar 

  6. Kolata, G. The New York Times May 5, p. 1 (1998).

    Google Scholar 

  7. King, R.T. Jr. The Wall St. Journal November 1, pA1 (1998 ).

    Google Scholar 

  8. Cohen,J. Science 283, 1250–1251 ( 1999).

    Article  CAS  Google Scholar 

  9. Folkman, J. Proc. Natl. Acad. Sci. USA 95, 9064– 9066 (1998).

    Article  CAS  Google Scholar 

  10. Crystal, R.G. Science 270, 404–410 ( 1995).

    Article  CAS  Google Scholar 

  11. Anderson, W.F. Nature 392 (suppl.), A25–A30 (1998).

    Article  Google Scholar 

  12. Ye, X. et al. Science 283, 88–91 ( 1999).

    Article  CAS  Google Scholar 

  13. Narumi, K. et al. Blood 92, 822–833 ( 1998).

    CAS  PubMed  Google Scholar 

  14. Suzuki, M. et al. Hum. Gene Ther 7, 1883–1893 (1996).

    Article  CAS  Google Scholar 

Download references

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  1. the Professor of Medicine in the Department of Medicine, Weill Medical College of Cornell University, New York, 10021, NY

    Ronald G. Crystal

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  1. Ronald G. Crystal
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Crystal, R. The body as a manufacturer of endostatin. Nat Biotechnol 17, 336–337 (1999). https://doi.org/10.1038/7890

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