Dynamic cell interaction with ECM components has profound influence in cancer 
progression. SPARC is a component of the ECM, impairs the proliferation of 
different cell types and modulates tumor cell aggressive features. We previously 
reported that SPARC expression significantly impairs medulloblastoma tumor 
growth in vivo. In this study, we demonstrate that expression of SPARC inhibits 
medulloblastoma cell proliferation. MTT assay indicated a dose-dependent 
reduction in tumor cell proliferation in adenoviral mediated expression of SPARC 
full length cDNA (Ad-DsRed-SP) in D425 and UW228 cells. Flow cytometric analysis 
showed that Ad-DsRed-SP-infected cells accumulate in the G2/M phase of cell 
cycle. Further, immunoblot and immunoprecipitation analyses revealed that SPARC 
induced G2/M cell cycle arrest was mediated through inhibition of the 
Cyclin-B-regulated signaling pathway involving p21 and Cdc2 expression. 
Additionally, expression of SPARC decreased STAT3 phosphorylation at Tyr-705; 
constitutively active STAT3 expression reversed SPARC induced G2/M arrest. 
Ad-DsRed-SP significantly inhibited the pre-established orthotopic tumor growth 
and tumor volume in nude-mice. Immunohistochemical analysis of tumor sections 
from mice treated with Ad-DsRed-SP showed decreased immunoreactivity for pSTAT3 
and increased immunoreactivity for p21 compared to tumor section from mice 
treated with mock and Ad-DsRed. Taken together our studies further reveal that 
STAT3 plays a key role in SPARC induced G2/M arrest in medulloblastoma cells. 
These new findings provide a molecular basis for the mechanistic understanding 
of the effects of SPARC on medulloblastoma tumor cell proliferation.