SPARC (secreted protein acidic and rich in cysteine)/BM40/Osteonectin is a 
matricellular protein with multiple effects on cell behaviour. In vitro, its 
major known functions are anti-adhesive and anti-proliferative, and it is 
associated with tissue remodelling and cancer in vivo. SPARC is overexpressed in 
many cancers, including breast cancer, and the effects of SPARC seem to be cell 
type-specific. To study the effects of SPARC on breast cancer, we transfected 
SPARC into the MDA-MB-231 BAG, human breast cancer cell line using the Tet-On 
inducible system. By western analysis, we found low background levels in the 
MDA-MB-231 BAG and clone X parental cells, and prominent induction of SPARC 
protein expression after doxycycline treatment in SPARC transfected clones X5, 
X21, X24 and X75. Induction of SPARC expression did not affect cell morphology 
or adhesiveness to collagens type I and IV, but it slowed the rate of 
proliferation in adherent cultures. Cell cycle analysis showed that SPARC slowed 
the progression to S phase. Doxycycline induction of SPARC also slowed the rate 
of monolayer wound closure in the cultured wound healing assay. Thymidine 
inhibition of proliferation abrogated this effect, confirming that it was due to 
anti-proliferation rather than inhibition of migration. Consistent with this, we 
were unable to detect any differences in migration and Matrigel outgrowth 
analysis of doxycycline-stimulated cells. We conclude that SPARC is inhibitory 
to human breast cancer cell proliferation, and does not stimulate migration, in 
contrast to its stimulatory effects reported for melanoma (proliferation and 
migration) and glioma (migration) cells. Similar growth repression by SPARC has 
been reported for ovarian cancer cells, and this may be a common feature among 
carcinomas.