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

Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-8593, USA.
American journal of obstetrics and gynecology (Impact Factor: 4.7). 12/2008; 200(2):180.e1-7. DOI: 10.1016/j.ajog.2008.08.047
Source: PubMed


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.
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.
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.
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.

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    • "As a result, it has been regarded as a therapeutic target for pancreatic adenocarcinoma [20] and gastric cancer [21] on the one hand, but as a therapeutic agent for colorectal [22,23] and ovarian [24] cancers on the other. Indeed, in ovarian cancer, SPARC has been shown to sensitize tumor cells to cisplatin therapy [24] and to enhance apoptosis and potentiate sensitivity to the chemotherapeutic agent 5-fluorouracil in colorectal cancer [23]. In the latter, this sensitivity was mediated by SPARC binding to procaspase 8. "
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