The exact mechanisms involved are not known, but SPARC is known to alter the expression of other genes.33 In addition, several reports show an inverse relationship between SPARC and VEGF expression; the more SPARC, the less VEGF, as well as the more VEGF, the less SPARC.43–46 Indeed, a study examining progression of serially passaged primary human glioma cells demonstrated that early passage tumor formation was accompanied by invasion, SPARC expression and no VEGF expression. The gene discussed is VEGFA; the disease is glioma.