SPARC has been found to act as an angiogenesis inhibitor by regulating the activities of growth factors like VEGF and platelet-derived growth factor [29–32]. While regulating VEGF, SPARC can bind to VEGF through EF-arm of the FS and EC areas to inhibit VEGF-stimulated proliferation of endothelial cells [7, 8, 33]. The role of slowing and terminating the tumor growth with SPARC by inhibiting the synthesis https://www.selleckchem.com/products/Temsirolimus.html and secretion of VEGF has been reported in glioma [34]. Similarly, Chlenski et al. [35] found that SPARC is an inhibitor

of angiogenesis in Schwann cells. They showed that MVD value of SPARC-treating group was significantly lower than non-treated control group and demonstrated that purified SPARC potently inhibited neuroblastoma growth and angiogenesis in vivo. In the current GSK458 in vitro study, from the expression pattern of SPARC and VEGF, we found that VEGF and SPARC were mainly expressed in tumor cells and MSC, respectively. The expression of the angiogenic factor VEGF and the intratumoral vascular density were apparently not related to the production of SPARC in MSC, however, high levels of

SPARC in MSC was significantly negative related with VEGF expression and MVD counts. In addition, our results showed that VEGF was significantly different with lymph node metastasis and TNM staging. VEGF expression was up-regulated in colon cancer along with the decreased expression of SPARC. All of these results suggest that SPARC may inhibit VEGF expression during the process of new blood vessel growth by which indirectly control the development, growth, invasion and metastasis of tumor cells in colon cancer. We also analyzed the relationships of SPARC and VEGF expression with clinical prognosis in this study. The results showed that patients with low expression of VEGF were survival longer than those with high expression for overall or disease-free survival evaluated by Kaplan-Meier

analysis. Similar results reported by Des et al. [1]. They investigated 27 kinds of VEGF expression in colorectal carcinoma using Meta analysis, and found that high levels of VEGF expression were related with unfavorable prognoses. Moreover, VEGFR inhibitor they revealed that VEGF was a more effective marker than MVD for prediction of overall survival in patients. We believe that increased expression of VEGF correlates with decreased SPARC expression. Reduction of SPARC may up-regulate the expression of VEGF, causing the subsequent MVD increase in tumors and resulting in a poor clinical outcome. Analysis for overall and disease-free survival showed that patients with low or absence of SPARC expression displayed a poor prognosis, when compared with patients with higher SPARC expression.