SPARC is a key Schwannian-derived inhibitor controlling neuroblastoma tumor angiogenesis.
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.
Chlenski
Alexandre
A
The Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611, USA.
Liu
Shuqing
S
Crawford
Susan E
SE
Volpert
Olga V
OV
DeVries
George H
GH
Evangelista
Amy
A
Yang
Qiwei
Q
Salwen
Helen R
HR
Farrer
Robert
R
Bray
James
J
Cohn
Susan L
SL
D000328:Adult; D020533:Angiogenesis Inhibitors / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D009447:Neuroblastoma / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D015676:Osteonectin / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D012583:Schwann Cells / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D015676:Osteonectin