Brook Naomi, Brook Emily, Dass Crispin R, Chan Arlene, Dharmarajan Arun
School of Pharmacy and Biomedical Science, Curtin University, Bentley, WA 6102, Australia.
Curtin Health Innovation Research Institute, Bentley, WA 6102, Australia.
Cancers (Basel). 2020 Nov 23;12(11):3483. doi: 10.3390/cancers12113483.
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.
雌激素和雄激素在正常组织和癌组织中发挥重要作用，并且已证实在性激素反应性肿瘤中它们对色素上皮衍生因子（PEDF）的表达具有负调控作用。PEDF可抑制肿瘤生长，雌激素对其表达的下调与肿瘤发生、转移及进展有关。与正常组织相比，前列腺、乳腺、卵巢及子宫内膜的癌组织中PEDF表达降低，临床前研究观察到PEDF下调与性激素信号传导之间存在关联。PEDF通过促进细胞凋亡、抑制血管生成、增强黏附及减少迁移来降低肿瘤细胞的生长和转移。PEDF还可能通过下调雌激素受体信号传导来预防某些癌症的治疗耐药性。通过与肿瘤微环境的成分相互作用，PEDF可抵消雌激素的增殖和免疫抑制作用，最终减少肿瘤发生和转移。在本综述中，我们重点关注性激素对PEDF在性激素反应性肿瘤中的抗肿瘤作用的调节。
