Cellular actions and signaling by endostatin.
The malignant transformation of a normal cell into a cancer cell requires no vasculature. Growth of solid tumors, however, requires angiogenesis to provide oxygen and nutrients to support cell proliferation. The switch from an avascular to a vascular phenotype is typically associated with acceleration of tumor growth. Antiangiogenic therapy, starving a tumor of its blood supply, is an attractive addition to the anticancer armamentarium. Animal tests of antiangiogenic therapy have shown remarkable potential. Initial human trials have proven antiangiogenic therapy to be remarkably nontoxic. Numerous antiangiogenic agents have been isolated as proteolytic fragments of endogenous polypeptides of the extracellular matrix. Endostatin was the first such antiangiogenic protein described and its potent antitumor effects in mice have generated wide interest. This review summarizes recent advances in endostatin biology and highlights new results on the cellular and subcellular mechanisms of endostatin action.
Ramchandran
Ramani
R
Division of Nephrology, Department of Medicine and Center for Study of the Tumor Microenvironment, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. rramchan@caregroup.harvard.edu
Karumanchi
S Ananth
SA
Hanai
Jun-ichi
J
Alper
Seth L
SL
Sukhatme
Vikas P
VP
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000378:metabolism; D003094:Collagen / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D043169:Endostatins; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D020533:Angiogenesis Inhibitors; D043169:Endostatins; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D003094:Collagen