Secreted protein acidic and rich in cysteine as a regulator of murine ovarian cancer growth and chemosensitivity

Shawna L. Bull Phelps, Juliet Carbon, Andrew Miller, Emely Castro-Rivera, Shanna Arnold, Rolf A. Brekken, Jayanthi S. Lea

Research output: Contribution to journalArticle

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Abstract

Objective: Secreted protein acidic and rich in cysteine (SPARC) influences the growth of several solid tumors. Our objectives were to determine the effect of SPARC on the growth and response to cisplatin therapy of platinum-resistant ovarian cancer. Study Design: SPARC expression was determined in 4 platinum-resistant ovarian cancer cell lines. The effect of increasing SPARC on cell proliferation was determined in vitro. The effect of host-derived SPARC on tumor growth and response to therapy was determined in vivo using the murine ovarian cancer cell line, OSEID8, which was injected into the peritoneum of wild-type (WT) and SPARC-null (SP-/-) mice. Results: Forced expression of SPARC decreased growth of platinum-resistant ovarian cancer cell lines in vitro. In vivo, tumor growth was more aggressive in the absence of host-derived SPARC resulting in decreased survival compared with WT mice (P = .005). Cisplatin did not improve survival of WT mice. In contrast, cisplatin therapy resulted in a significant survival advantage (P = .0048) and decreased tumor volume (P = .02) in SP-/- animals. Conclusion: We conclude that SPARC is an important extracellular matrix protein that regulates the growth and chemosensitivity of ovarian cancer. In general, SPARC appears to control tumor cell growth but also impede the efficacy of cisplatin therapy. Therefore, selective inhibition of SPARC may provide an attractive strategy for increasing the efficacy of therapy in platinum-resistant ovarian tumors.

Original languageEnglish (US)
JournalAmerican Journal of Obstetrics and Gynecology
Volume200
Issue number2
DOIs
StatePublished - Feb 2008

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Ovarian Neoplasms
Cysteine
Growth
Proteins
Platinum
Cisplatin
Neoplasms
Cell Line
Therapeutics
Extracellular Matrix Proteins
Peritoneum
Tumor Burden
Cell Proliferation

Keywords

  • Chemosensitivity
  • extracellular matrix
  • murine
  • ovarian cancer
  • secreted protein acidic and rich in cysteine

ASJC Scopus subject areas

  • Obstetrics and Gynecology

Cite this

Secreted protein acidic and rich in cysteine as a regulator of murine ovarian cancer growth and chemosensitivity. / Bull Phelps, Shawna L.; Carbon, Juliet; Miller, Andrew; Castro-Rivera, Emely; Arnold, Shanna; Brekken, Rolf A.; Lea, Jayanthi S.

In: American Journal of Obstetrics and Gynecology, Vol. 200, No. 2, 02.2008.

Research output: Contribution to journalArticle

Bull Phelps, Shawna L. ; Carbon, Juliet ; Miller, Andrew ; Castro-Rivera, Emely ; Arnold, Shanna ; Brekken, Rolf A. ; Lea, Jayanthi S. / Secreted protein acidic and rich in cysteine as a regulator of murine ovarian cancer growth and chemosensitivity. In: American Journal of Obstetrics and Gynecology. 2008 ; Vol. 200, No. 2.
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