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Our initial basement membrane degradome screen using Cathepsin D, a tumor microenvironment\u2013associated protease, contained fragments of fibulin-1 and full length fibulin-5. In this report, we evaluate the antiangiogenic activity of fibulin-1 and fibulin-5. Tumor studies demonstrate that both fibulin-1 and fibulin-5 suppress HT1080 tumor growth. CD31 labeling and TUNEL assay further reveal that fibulin-1 suppression of HT1080 tumor growth is associated with diminished angiogenesis and also enhanced apoptosis of endothelial cells and tumor cells. In contrast, fibulin-5 inhibits tumor angiogenesis with a minimal anti-apoptotic affect. Cathepsin D digestion of fibulin-1 produces a fragment with nearly the same molecular weight as fibulin-5, and this fragment (named Neostatin) inhibits endothelial cell proliferation. Additionally, degradation of basement membrane by cathepsin D liberates both fibulin-1 fragments and fibulin-5, which function to inhibit angiogenesis. <\/jats:p>","DOI":"10.3181\/0706-rm-167","type":"journal-article","created":{"date-parts":[[2008,5,12]],"date-time":"2008-05-12T23:11:21Z","timestamp":1210633881000},"page":"155-162","source":"Crossref","is-referenced-by-count":51,"title":["Basement Membrane Derived Fibulin-1 and Fibulin-5 Function as Angiogenesis Inhibitors and Suppress Tumor Growth"],"prefix":"10.3389","volume":"233","author":[{"given":"Liang","family":"Xie","sequence":"first","affiliation":[{"name":"Division of Matrix Biology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215; Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, MA 02115; Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02215; and Harvard-MIT Division of Health Sciences and Technology, Boston, MA 02215"}]},{"given":"Kristin","family":"Palmsten","sequence":"additional","affiliation":[{"name":"Division of Matrix Biology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215; Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, MA 02115; Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02215; and Harvard-MIT Division of Health Sciences and Technology, Boston, MA 02215"}]},{"given":"Brian","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Division of Matrix Biology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215; Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, MA 02115; Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02215; and Harvard-MIT Division of Health Sciences and Technology, Boston, MA 02215"}]},{"given":"Mark W.","family":"Kieran","sequence":"additional","affiliation":[{"name":"Division of Matrix Biology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215; Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, MA 02115; Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02215; and Harvard-MIT Division of Health Sciences and Technology, Boston, MA 02215"}]},{"given":"Scott","family":"Potenta","sequence":"additional","affiliation":[{"name":"Division of Matrix Biology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215; Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, MA 02115; Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02215; and Harvard-MIT Division of Health Sciences and Technology, Boston, MA 02215"}]},{"given":"Sylvia","family":"Vong","sequence":"additional","affiliation":[{"name":"Division of Matrix Biology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215; Department of Pediatric Oncology, Dana Farber Cancer Institute, Boston, MA 02115; Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02215; and Harvard-MIT Division of Health Sciences and Technology, Boston, MA 02215"}]},{"given":"Raghu","family":"Kalluri","sequence":"additional","affiliation":[{"name":"Division of Matrix Biology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215; 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