The degrees of its expression were associated with differentiation of tumor, TNM division, peritoneal seeding and vascular invasion remarkably. Patients with high expression of SPARC have worse prognosis than those with low expression of SPARC. Taken together, higher SPARC expression was significantly associated with tumour progression and advanced stages of gastric cancer. Recent research of Inoue M et al[23] even identifed SPARC as a candidate target antigen for immunotherapy of various cancers including gastric cancer by genome-wide cDNA microarray. It is exciting that therapy targeting the SPARC subunit may be a useful find more approach to suppress gastric cancer growth. However, the molecular

mechanisms Pexidartinib responsible for the oncogenesis of SPARC in gastric cancer is not entirely understood. Through expression analysis of a panel of gastric cancer cell lines, we showed that SPARC is also overexpressed in sevel human gastric cancer cell lines. Therefore, we tested our hypotheses that SPARC may be a key molecule in gastric cancer invasion, and that targeting SPARC may present a novel therapeutic strategy for anti-invasion of gastric cancer. Dissemination of cancer cells, either locally or at distant metastatic sites, requires that malignant cells acquire the ability

to invade the basement membrane and to adhere to other matrices. It has been suggested that SPARC may play a key role during the initial steps in the process of tumour invasion and metastasis[24]. In addition, SPARC can induce the expression of metalloproteinases or enzymes that subsequently play an important role in the degradation

of basal membranes and extracellular matrix components[25]. SPARC was associated with the invasiveness of meningiomas[26, 27] and gliomas[28]. Furthermore, suppression of SPARC expression using antisense RNA inhibited motility and invasion of human breast cancer cells in vitro[21]. To determine if SPARC siRNA could reduce protumorigenic cellular behaviors associated with SPARC expression, we first determined the effect of decreased SPARC expression on tumor cell invasion. We measured the capacity Fludarabine research buy of gastric cancer cells to invade through Matrigel, an artificial extracellular matrix, after transfection with SPARC siRNA or a non-targeting control siRNA. Decreased SPARC expression led to the inhibition of invasion by 69% and 79% in MGC803 and HGC27, respectively. Thus, SPARC siRNA can decrease gastric cancer invasion in vitro. A recent study found that SPARC protects cells from stress-induced apoptosis in vitro through an interaction with integrin β1 heterodimers that enhance ILK activation and prosurvival activity[28]. Initial studies using antisense RNA strategies completely abrogated human melanoma growth in nude mice[21]. Horie et al.[29] showed that the downregulation of SPARC expression induced growth inhibition with G1 arrest in human melanoma cells.