New study below.
Pigment epithelium-derived factor [PEDF] is new to me, but there are now 25 PCa-PEDF hits on PubMed (beginning 2003).
The first (1) identified PEDF "as a key inhibitor of stromal vasculature and epithelial tissue growth in mouse prostate".
Study (2) reported that "loss of pigment epithelium-derived factor expression could be associated with the progression toward a metastatic phenotype in prostate cancer"
From (3): "PEDF apparently has multiple effects in prostate tumors: it suppresses angiogenesis and metastasis, but it also causes macrophage accumulation. Accumulating macrophages may inhibit tumor growth, but they may also suppress PEDF and enhance lymph angiogenesis and, in this way, eventually enhance tumor growth."
(4) "Pigment epithelium-derived factor expression prolongs survival and enhances the cytotoxicity of low-dose chemotherapy in castration-refractory prostate cancer"
In the new study (5):
"We hypothesized that the antitumorigenic effects of metformin are mediated through upregulation of pigment epithelium-derived factor (PEDF) expression in prostate cancer cells."
"... Metformin markedly suppressed migration and invasion and induced apoptosis of both LNCaP and PC3 cancer cells. Metformin also reduced PC3 tumor growth in BALB/c nude mice in vivo."
"Furthermore, metformin treatment was associated with higher PEDF expression in both prostate cancer cells and tumor tissue."
"These findings provide a novel insight into the molecular functions of metformin as an anticancer agent."