Pigment Epithelium-Derived Factor and Sex Hormone-Responsive Cancers

SIMPLE SUMMARY: The ongoing clinical need to improve cancer therapies warrants a better understanding of the mechanisms behind cancer growth and its spread to distant organs. To this end, research into the impact of sex hormones, such as oestrogens and testosterones, in cancers has led to improvements in the way sex hormone-responsive cancers are treated. Pigment epithelium-derived factor (PEDF) is a protein with anti-cancer properties that is also sensitive to sex hormones. The aim of this review is to explore what is currently known about sex hormones and PEDF in cancers in order to better understand the anti-cancer role of PEDF in sex hormone-responsive cancers. ABSTRACT: Oestrogens and androgens play important roles in normal and cancerous tissue and have been shown to negatively regulate pigment epithelium-derived factor (PEDF) expression in sex hormone-responsive tumours. PEDF suppresses tumour growth and its downregulation by oestrogen is implicated in tumorigenesis, metastasis, and progression. PEDF expression is reduced in cancerous tissue of the prostate, breast, ovary, and endometrium compared to their normal tissue counterparts, with a link between PEDF downregulation and sex hormone signalling observed in pre-clinical studies. PEDF reduces growth and metastasis of tumour cells by promoting apoptosis, inhibiting angiogenesis, increasing adhesion, and reducing migration. PEDF may also prevent treatment resistance in some cancers by downregulating oestrogen receptor signalling. By interacting with components of the tumour microenvironment, PEDF counteracts the proliferative and immunosuppressive effects of oestrogens, to ultimately reduce tumorigenesis and metastasis. In this review, we focus on sex hormone regulation of PEDF’s anti-tumour action in sex hormone-responsive tumours.