文章：

类二十烷酸和癌症

Eicosanoids and cancer

原文发布日期：2010-02-19

DOI: 10.1038/nrc2809

类型: Review Article

开放获取: 否

要点：

1. The altered metabolism of arachidonic acid by cyclooxygenase (COX) and lipoxygenase (LOX) is a common feature of several epithelial-derived malignancies and has been shown to have crucial roles in cancer progression.
2. The production of arachidonic acid-derived prostanoids and leukotrienes occurs in single cells or takes place in a complex manner in which these biologically active lipids, specifically leukotrienes, are generated by transcellular biosynthesis through the cooperation of multiple different types of cells in the tumour and inflamed tissues.
3. Pro-inflammatory prostaglandins and leukotrienes promote tumour growth by regulating tumour epithelial cells themselves and orchestrating the complex interactions between transformed epithelial cells and surrounding stromal cells to establish the tumour microenvironment that facilitates tumour-associated angiogenesis and evades attack by the immune system.
4. Prostaglandins and leukotrienes can modulate tumour epithelial cell proliferation, apoptosis, and migration and invasion through multiple signalling pathways in both an autocrine and paracrine fashion.
5. Prostaglandins and leukotrienes are central molecules in the regulation of stem cell homeostasis.
6. Pro-inflammatory prostaglandins and leukotrienes are key mediators in the crosstalk between tumour epithelial cells and their surrounding stromal cells in establishing a tumour microenvironment with chronic inflammation and immunosuppression.
7. Although non-steroidal anti-inflammatory drugs (NSAIDs), which target COX enzymes, are still among the most promising chemopreventive agents for cancer, cardiovascular and gastrointestinal side effects have dampened enthusiasm for their use as chemopreventive agents. Understanding the roles of prostaglandins and leukotrienes in epithelial-derived tumours and their microenvironment may help to develop cancer biomarkers and chemopreventive and/or therapeutic agents with a greater benefit and fewer side effects than NSAIDs.

要点翻译：

1. 花生四烯酸通过环氧合酶（COX）和脂氧合酶（LOX）发生的代谢改变是多种上皮源性恶性肿瘤的共同特征，并已被证明在癌症进展中起关键作用。
2. 花生四烯酸衍生的前列腺素和白三烯的产生可在单细胞内发生，或以复杂方式进行——这些生物活性脂质（特别是白三烯）通过肿瘤和炎症组织中多种不同类型细胞的协同作用，经跨细胞生物合成途径生成。
3. 促炎性前列腺素和白三烯通过调节肿瘤上皮细胞自身，并协调转化上皮细胞与周围基质细胞之间的复杂相互作用来促进肿瘤生长，从而建立有利于肿瘤相关血管生成并逃避免疫系统攻击的肿瘤微环境。
4. 前列腺素和白三烯可通过自分泌和旁分泌方式，经由多条信号通路调控肿瘤上皮细胞的增殖、凋亡、迁移和侵袭。
5. 前列腺素和白三烯是调节干细胞稳态的核心分子。
6. 在建立具有慢性炎症和免疫抑制特性的肿瘤微环境过程中，促炎性前列腺素和白三烯是肿瘤上皮细胞与其周围基质细胞间通讯的关键介质。
7. 尽管靶向COX酶的非甾体抗炎药（NSAIDs）仍是最有前景的癌症化学预防药物之一，但其心血管和胃肠道副作用削弱了其作为化学预防药物的应用热情。深入了解前列腺素和白三烯在上皮源性肿瘤及其微环境中的作用，有助于开发比NSAIDs获益更大、副作用更少的癌症生物标志物及化学预防和/或治疗药物。

英文摘要：

Eicosanoids, including prostaglandins and leukotrienes, are biologically active lipids that have been implicated in various pathological processes, such as inflammation and cancer. This Review highlights our understanding of the intricate roles of eicosanoids in epithelial-derived tumours and their microenvironment. The knowledge of how these lipids orchestrate the complex interactions between transformed epithelial cells and the surrounding stromal cells is crucial for understanding tumour evolution, progression and metastasis. Understanding the molecular mechanisms underlying the role of prostaglandins and other eicosanoids in cancer progression will help to develop more effective cancer chemopreventive and/or therapeutic agents.

摘要翻译： 

包括前列腺素和白三烯在内的类二十烷酸是具有生物活性的脂质，已被证实参与炎症和癌症等多种病理过程。本综述强调了我们对类二十烷酸在上皮源性肿瘤及其微环境中复杂作用的理解。了解这些脂质如何调控转化上皮细胞与周围基质细胞之间的复杂相互作用，对于理解肿瘤的发生、进展和转移至关重要。阐明前列腺素及其他类二十烷酸在癌症进展中作用的分子机制，将有助于开发更有效的癌症化学预防和/或治疗药物。

原文链接：

Eicosanoids and cancer