RRC ID 76353
Author Horie K, Tsuchihara M, Nakatsura T.
Title Silencing of secreted protein acidic and rich in cysteine inhibits the growth of human melanoma cells with G arrest induction.
Journal Cancer Sci
Abstract 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.
Volume 101(4)
Pages 913-9
Published 2010-4-1
DOI 10.1111/j.1349-7006.2009.01476.x
PMID 20100207
MeSH Animals Apoptosis / genetics Cell Line, Tumor Cell Proliferation Female G1 Phase Humans Melanoma / genetics Melanoma / metabolism* Melanoma / pathology* Mice Mice, Nude Neoplasm Transplantation Osteonectin / genetics Osteonectin / physiology* RNA, Small Interfering / genetics Skin Neoplasms / genetics Skin Neoplasms / metabolism* Skin Neoplasms / pathology*
IF 4.966
Human and Animal Cells C32TG(RCB1929)