文章：

PEDF对癌症生物学的影响：作用机制和治疗潜力

The effects of PEDF on cancer biology: mechanisms of action and therapeutic potential

原文发布日期：2013-03-14

DOI: 10.1038/nrc3484

类型: Review Article

开放获取: 否

要点：

1. PEDF is a member of the serpin superfamily that has many functions that often act in opposition to mechanisms that drive cancer progression.
2. Tumour progression is associated with reduced levels of PEDF in tumours. Exogenous administration of PEDF to bolster the declining intratumoural levels of PEDF during tumour progression results in the inhibition of tumour growth and prolonged organismal survival in various animal models.
3. PEDF can act directly on tumours to induce differentiation to a less-malignant phenotype, promote apoptotic tumour cell death and inhibit the proliferation of tumour cells.
4. Numerous studies in various models have shown the anti-angiogenic effects that PEDF has on tumours. PEDF is a potent inhibitor of angiogenesis through pro-apoptotic effects on endothelial cells. It can also inhibit endothelial cell migration, endothelial tube formation, vessel sprouting and intratumoural neovascularization, and can decrease the levels of pro-angiogenic factors.
5. Support for its anticancer role also comes from the findings that PEDF exhibits strong antimetastatic activity by suppressing tumour cell invasion and migration; these effects have been described in vitro and in several metastasis models in vivo.
6. The molecular mechanisms by which PEDF functions to regulate tumour and endothelial cell behaviour are based mostly on its interactions with different cell-surface receptors and their downstream signalling pathways.
7. PEDF abundance and activities are regulated both by extrinsic microenvironment-altering effectors (such as hormones, vitamins, oxygenation or extracellular matrix (ECM) composition), as well as by molecular drivers that alter its intrinsic properties (such as post-translational modifications).
8. Numerous reports have provided evidence in support of the use of PEDF as a prognostic factor in cancer management. PEDF-positive expression is described as an independent favourable prognostic factor for cancer.

要点翻译：

1. 色素上皮衍生因子（PEDF）是丝氨酸蛋白酶抑制剂超家族成员，具有多种常与癌症进展驱动机制相拮抗的功能。
2. 肿瘤进展与瘤体内PEDF水平降低相关。在多种动物模型中，外源性补充PEDF以提升肿瘤进展过程中逐渐降低的瘤内PEDF水平，可抑制肿瘤生长并延长机体存活时间。
3. PEDF可直接作用于肿瘤，诱导其分化为恶性程度较低的表型，促进肿瘤细胞凋亡性死亡，并抑制肿瘤细胞增殖。
4. 多种模型中的大量研究揭示了PEDF对肿瘤的抗血管生成作用。通过对内皮细胞的前凋亡作用，PEDF成为血管生成的强效抑制剂。它还能抑制内皮细胞迁移、内皮管形成、血管出芽及瘤内新生血管形成，并降低促血管生成因子水平。
5. 其抗癌作用还得到以下发现的支持：PEDF通过抑制肿瘤细胞侵袭和迁移展现出强效抗转移活性，这些效应已在体外实验及多种体内转移模型中得到验证。
6. PEDF调控肿瘤和内皮细胞行为的分子机制主要基于其与不同细胞表面受体及下游信号通路的相互作用。
7. PEDF的丰度和活性既受外在微环境改变效应物（如激素、维生素、氧合作用或细胞外基质成分）调控，也受改变其内在特性的分子驱动因子（如翻译后修饰）调节。
8. 大量研究证据支持将PEDF作为癌症管理的预后因素，PEDF阳性表达被确定为独立的有利癌症预后因子。

英文摘要：

The potent actions of pigment epithelium-derived factor (PEDF) on tumour-associated cells, and its extracellular localization and secretion, stimulated research on this multifunctional serpin. Such studies have identified several PEDF receptors and downstream signalling pathways. Known cellular PEDF responses have expanded from the initial discovery that PEDF induces retinoblastoma cell differentiation to its anti-angiogenic, antitumorigenic and antimetastatic properties. Although the diversity of PEDF activities seems to be complex, they are consistent with the varied mechanisms that regulate this multimodal factor. If PEDF is to be used for cancer management, a deeper appreciation of its many functions and mechanisms of action is needed.

摘要翻译： 

色素上皮衍生因子（PEDF）对肿瘤相关细胞的强效作用，以及其细胞外定位和分泌特性，激发了对这种多功能丝氨酸蛋白酶抑制剂的研究。此类研究已鉴定出多种PEDF受体及其下游信号通路。已知的细胞PEDF反应从最初的发现——即PEDF能诱导视网膜母细胞瘤细胞分化——扩展到其抗血管生成、抗肿瘤发生和抗转移的特性。尽管PEDF活性的多样性看似复杂，但它们与调控这一多模式因子的多种机制是一致的。若要将PEDF用于癌症治疗，则需更深入地理解其多重功能及作用机制。

原文链接：

The effects of PEDF on cancer biology: mechanisms of action and therapeutic potential