Down-Regulation of Placenta Growth Factor by Promoter Hypermethylation in Human Lung and Colon Carcinoma

Abstract

Two recent clinical trials have shown that the placenta growth factor (PlGF) is up-regulated after bevacizumab treatment in colorectal cancer and after SU11248 treatment in metastatic renal cell carcinoma.

Epigenetic control of hypoxia inducible factor-1α-dependent expression of placental growth factor in hypoxic conditions

“…To date, only one previous study has investigated Plgf promoter methylation. 45 Interestingly, this study reported that hypermethylation of the Plgf promoter is associated with PlGF downregulation in human lung and colon carcinoma tissues, as well as in correspondent cancer cell lines in normoxic conditions, suggesting that the methylation of the Plgf promoter may change in different cell and tissue contexts.…”

PlGF: A Multitasking Cytokine with Disease-Restricted Activity

“…Exceptions include colon and lung carcinoma, where PlGF expression is low because of epigenetic silencing (Xu and Jain 2007). Not only can the tumor cells themselves produce PlGF, but also most types of stromal cells, including endothelial cells, smooth muscle cells, pericytes, cancerassociated fibroblasts (CAFs), tumor-associated macrophages (TAMs), and inflammatory cells (Yonekura et al 1999;Carmeliet et al 2001;Luttun et al 2002;Fischer et al 2007;Bagley et al 2011;Rolny et al 2011).…”

“Antimyeloangiogenic” Therapy for Cancer by Inhibiting PlGF

“…Plasma PlGF levels are also correlated with tumor stage and survival in renal cancer (40). Of note, reported PlGF expression levels indicate some variance, such as absence of detectable PlGF in ovarian tumors (41) or low expression levels due to epigenetic silencing of the PlGF promotor in colorectal cancer (42). This variance might be due to the spectrum of experimental methods used warranting more research with larger cohorts and homogenous analytical methods.…”