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


METHODS
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.


CONCLUSIONS
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.
Bull Phelps
Shawna L
SL
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-8593, USA.
Carbon
Juliet
J
Miller
Andrew
A
Castro-Rivera
Emely
E
Arnold
Shanna
S
Brekken
Rolf A
RA
Lea
Jayanthi S
JS
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm; D005260:Female; D051379:Mice; D015676:Osteonectin / Q000096:biosynthesis / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism*
D015676:Osteonectin