Affiliation:
1. From the Edwin L. Steele Laboratory for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA; and the Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA.
Abstract
Abstract
The traditional view of angiogenesis emphasizes proliferation and migration of vessel wall-associated endothelial cells. However, circulating endothelial progenitor cells have recently been shown to contribute to tumor angiogenesis. Here we quantify the relative contributions of endothelial and endothelial progenitor cells to angiogenesis using a mathematical model. The model predicts that during the early stages of tumor growth, endothelial progenitors have a significant impact on tumor growth and angiogenesis, mediated primarily by their localization in the tumor, not by their proliferation. The model also shows that, as the tumor grows, endothelial progenitors adhere preferentially near the tumor periphery, coincident with the location of highest vascular density, supporting their potential utility as vectors for targeted delivery of therapeutics. Model simulations of various antiangiogenic strategies show that those therapies that effectively target both endothelial and endothelial progenitor cells, either by restoring the balance between angiogenic stimulators and inhibitors or by targeting both types of cells directly, are most effective at delaying tumor growth. The combination of continuous low-dose chemotherapy and antiangiogenic therapy is predicted to have the most significant effect on therapeutic outcome. The model offers new insight into tumor angiogenesis with implications for the rational design of antiangiogenic therapy. (Blood. 2003;102:2555-2561)
Publisher
American Society of Hematology
Subject
Cell Biology,Hematology,Immunology,Biochemistry
Reference45 articles.
1. Folkman J. Angiogenesis. In: Braunwald AS, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL, eds. Harrison's Principles of Internal Medicine. 15th ed. New York, NY: McGraw-Hill; 2001: 517-530.
2. Kerbel RS. Tumor angiogenesis: past, present and the near future. Carcinogenesis. 2000;21: 505-515.
3. Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature. 2000;407: 249-257.
4. Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science. 1997;275: 964-967.
5. Rafii S, Lyden D, Benezra R, Hattori K, Heissig B. Vascular and haematopoietic stem cells: novel targets for anti-angiogenesis therapy? Nature Rev Cancer. 2002;2: 826-835.
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