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[Cancer Research 62, 7357-7363, December 15, 2002]
© 2002 American Association for Cancer Research

Tumor Biology

SPARC Is a Key Schwannian-derived Inhibitor Controlling Neuroblastoma Tumor Angiogenesis1

Alexandre Chlenski, Shuqing Liu, Susan E. Crawford, Olga V. Volpert, George H. DeVries, Amy Evangelista, Qiwei Yang, Helen R. Salwen, Robert Farrer, James Bray and Susan L. Cohn2

Departments of Pediatrics [S. L. C.] and Pathology [S. E. C.] and The Robert H. Lurie Comprehensive Cancer Center [A. C., S. L., O. V. V., A. E., Q. Y., H. R. S., J. B.], Northwestern University, Feinberg School of Medicine, Chicago, Illinois 60611, and the Department of Cell Biology, Neurobiology, and Anatomy, Loyola University of Chicago Stritch School of Medicine, Chicago, Illinois 60153 [G. H. D., R. F.]

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.




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Copyright © 2002 by the American Association for Cancer Research.