SPARC is a key schwannian-derived inhibitor controlling neuroblastoma tumor angiogenesis

• Published in: Cancer research (Chicago, Ill.) Vol. 62; no. 24; pp. 7357 - 7363
• Main Authors: CHLENSKI, Alexandre, SHUQING LIU, COHN, Susan L, CRAWFORD, Susan E, VOLPERT, Olga V, DEVRIES, George H, EVANGELISTA, Amy, QIWEI YANG, SALWEN, Helen R, FARRER, Robert, BRAY, James
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.12.2002
• Subjects: Adult; Angiogenesis Inhibitors - biosynthesis; Angiogenesis Inhibitors - pharmacology; Angiogenesis Inhibitors - physiology; Angiogenesis Inhibitors - secretion; Animals; Antineoplastic agents; Biological and medical sciences; Cell Differentiation - physiology; Cell Division - physiology; Cell Movement - drug effects; Chemotherapy; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Female; Humans; Medical sciences; Mice; Mice, Nude; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - pathology; Neuroblastoma - blood supply; Neuroblastoma - metabolism; Neuroblastoma - pathology; Osteonectin - biosynthesis; Osteonectin - pharmacology; Osteonectin - physiology; Osteonectin - secretion; Pharmacology. Drug treatments; Schwann Cells - metabolism; Schwann Cells - secretion; Xenograft Model Antitumor Assays; Antineoplastic agent; Cell proliferation; Endothelial cell; Rat; Neuroblastoma; Angiogenesis; Schwann cell; Established cell line; Neovascularization; Antiangiogenic agent; Human; Nervous system diseases; Rodentia; Malignant tumor; In vitro; Biological activity; In vivo; Vertebrata; Chemotherapy; Mammalia; Treatment; Mouse; Animal; Inhibitor; Autonomic neuropathy
• ISSN: 0008-5472; 1538-7445

Neuroblastoma (NB), a common pediatric neoplasm, consists of two main cell populations: neuroblastic/ganglionic cells and Schwann cells. NB tumors with abundant Schwannian stroma display a more benign clinical behavior than stroma-poor tumors. Recent studies suggest that Schwann cells influence NB tumor growth via secreted factors that induce differentiation, suppress proliferation, and inhibit angiogenesis. Two angiogenesis inhibitors, pigment epithelium-derived factor and tissue inhibitor of metalloproteinase-2, have been detected in Schwann cell secretions. Here, we isolated another Schwann cell-derived secreted inhibitor of angiogenesis, a 43-kDa protein identified as SPARC (secreted protein acidic and rich in cysteine), an extracellular matrix protein. We found SPARC to be critical for the antiangiogenic phenotype of cultured Schwann cells. We also show that purified SPARC potently inhibits angiogenesis and significantly impairs NB tumor growth in vivo. SPARC may be an effective candidate for the treatment of children with clinically aggressive, Schwannian stroma-poor NB tumors.