The overexpression of secreted protein acidic and rich in cysteine (SPARC) is 
associated with increased aggressiveness and poor prognosis in malignant 
melanoma. Its roles and underlying mechanisms on melanoma cell growth, however, 
are not fully clarified. To validate the potential of SPARC as a therapeutic 
target, we examined the effect of the knockdown of SPARC with SPARC-specific 
siRNA on the growth of human melanoma cell lines. SPARC siRNAs exerted a potent 
knockdown effect. Silencing of SPARC resulted in growth inhibition with G(1) 
arrest accompanied by accumulation of p21, a G(1) cyclin-dependent kinase 
inhibitor, in MeWo and CRL1579 cells. Moreover, the induction of p53 was 
observed in MeWo cells, but not in CRL1579 cells. Conditioned media containing 
SPARC from MeWo cells could not restore the growth of SPARC-silenced MeWo cells. 
This result suggests that intracellular SPARC, but not secreted SPARC, is 
involved in cell proliferation. In addition, silencing of SPARC induced 
apoptosis in MeWo and CRL1579 cells. Furthermore, when MeWo cells in which SPARC 
expression was transiently knocked down by SPARC siRNA were implanted in nude 
mice, the tumor growth was suppressed. Our findings suggest that SPARC 
contributes to cell growth and could be a potential target molecule for melanoma 
therapy.