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

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

Research output: Contribution to journalArticle

132 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)7357-7363
Number of pages7
JournalCancer Research
Volume62
Issue number24
Publication statusPublished - Dec 15 2002

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Chlenski, A., Liu, S., Crawford, S. E., Volpert, O. V., DeVries, G. H., Evangelista, A., ... Cohn, S. L. (2002). SPARC is a key Schwannian-derived inhibitor controlling neuroblastoma tumor angiogenesis. Cancer Research, 62(24), 7357-7363.