SPARC expression is associated with impaired tumor growth, inhibited angiogenesis and changes in the extracellular matrix

Alexandre Chlenski, Shuqing Liu, Lisa J. Guerrero, Qiwei Yang, Yufeng Tian, Helen R. Salwen, Peter Zage, Susan L. Cohn

Research output: Contribution to journalArticle

88 Scopus citations

Abstract

Secreted protein, acidic and rich in cysteine (SPARC), is a multifunctional matricellular glycoprotein. In vitro, SPARC has antiangiogenic properties, including the ability to inhibit the proliferation and migration of endothelial cells stimulated by bFGF and VEGF. Previously, we demonstrated that platelet-derived SPARC also inhibits angiogenesis and impairs the growth of neuroblastoma tumors in vivo. In the present study, we produced rhSPARC in the transformed human embryonic kidney cell line 293 and show that the recombinant molecule retains its ability to inhibit angiogenesis. Although 293 cell proliferation was not affected by exogenous expression of SPARC in vitro, growth of tumors formed by SPARC-transfected 293 cells was significantly impaired compared to tumors comprised of wild-type cells or 293 cells transfected with a control vector. Consistent with its function as an angiogenesis inhibitor, significantly fewer blood vessels were seen in SPARC-transfected 293 tumors compared to controls, and these tumors contained increased numbers of apoptotic cells. Light microscopy revealed small nests of tumor cells surrounded by abundant stromal tissue in xenografts with SPARC expression, whereas control tumors were comprised largely of neoplastic cells with scant stroma. Mature, covalently cross-linked collagen was detected in SPARC-transfected 293 xenografts but not in control tumors. Our studies suggest that SPARC may regulate tumor growth by inhibiting angiogenesis, inducing tumor cell apoptosis and mediating changes in the deposition and organization of the tumor microenvironment.

Original languageEnglish (US)
Pages (from-to)310-316
Number of pages7
JournalInternational Journal of Cancer
Volume118
Issue number2
DOIs
StatePublished - Jan 15 2006

Keywords

  • Angiogenesis
  • Collagen
  • Neuroblastoma
  • SPARC
  • Transglutaminase
  • Tumor growth

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Chlenski, A., Liu, S., Guerrero, L. J., Yang, Q., Tian, Y., Salwen, H. R., Zage, P., & Cohn, S. L. (2006). SPARC expression is associated with impaired tumor growth, inhibited angiogenesis and changes in the extracellular matrix. International Journal of Cancer, 118(2), 310-316. https://doi.org/10.1002/ijc.21357