SPARC has been reported to be markedly down-regulated in ovarian carcinomas relative to the normal surface epithelium and has been suggested to act as a tumor suppressor in ovarian cancer.
These results indicate, for the first time, that the effects of tumor SPARC as a negative regulator of ovarian cancer are mediated through decreased recruitment of macrophages and downregulation of the associated inflammation.
Investigation of primary tumors revealed that the Sparc promoter is methylated in 68% of primary ovarian tumors and that the levels of SPARC protein decrease as the disease progresses from low to high grade.
These results suggest SPARC might function as a tumor suppressor inhibiting angiogenesis and lymphangiogenesis in ovarian cancer by reducing the expression of VEGF-C and VEGF-D.
We used a syngeneic model of OvCa in <i>Sparc</i>-deficient and proficient mice to gain comprehensive insight into the paracrine effect of stromal-SPARC in metabolic programming of OvCa in the peritoneal milieu.
These findings define a novel and functionally important role of SPARC in OvCa and not only bridge the knowledge gap but highlight the need to consider SPARC protein expression in therapeutic development.