文章：

卵巢癌转移：整合来自不同模式生物的见解

Ovarian Cancer Metastasis: Integrating insights from disparate model organisms

原文发布日期：2005-05-01

DOI: 10.1038/nrc1611

类型: Review Article

开放获取: 否

要点：

1. The lethality of ovarian carcinoma primarily stems from the inability to detect the disease at an early, organ-confined stage, and the lack of effective therapies for advanced-stage disease. So there is a need for new therapeutic targets and a better understanding of the mechanisms involved in the spread of ovarian carcinoma.
2. A widely recognized behaviour of ovarian carcinoma is its ability to seed the peritoneal cavity with nests of tumour cells and the formation of ascites. Vascular endothelial growth factor (or vascular permeability factor) is an important factor that promotes ascites accumulation.
3. The motility and invasive behaviour of ovarian carcinoma cells are regulated by a repertoire of signalling pathways, several components of which have been evaluated as therapeutic targets in preclinical models and in clinical trials. The identification of new molecular targets might lead to new therapies.
4. Border cells in the Drosophila melanogaster ovary are motile and invasive somatic cells that share some characteristics with ovarian carcinoma cells. Genetic analysis in this simple organism has resulted in the identification of many proteins that contribute to the timing and guidance of border-cell migration.
5. Based on the work in D. melanogaster, the functions of some mammalian proteins, such as myosin VI, have been tested for their ability to regulate motility of ovarian carcinoma cells.
6. An inhibitor of apoptosis protein has been found to promote border-cell migration, in addition to its well-known function in preventing cell death, highlighting the intimate connection between cell survival and motility.
7. The finding that many molecules that promote cell motility also increase resistance to natural or chemotherapy-induced cell death provides a possible molecular basis for the observation that metastatic disease is more resistant to treatment.

要点翻译：

1. 卵巢癌的致命性主要源于两大因素：一是无法在早期器官局限阶段检测出疾病，二是对晚期疾病缺乏有效疗法。因此需要寻找新的治疗靶点，并更深入地理解卵巢癌扩散的机制。
2. 卵巢癌的一个广为人知的特征是它能够在腹膜腔播散肿瘤细胞团并形成腹水。血管内皮生长因子（又称血管通透性因子）是促进腹水积聚的重要因素。
3. 卵巢癌细胞的运动性和侵袭行为受多种信号通路调控，其中若干组分已在临床前模型和临床试验中作为治疗靶点进行评估。新分子靶点的发现可能催生新的疗法。
4. 黑腹果蝇卵巢中的边界细胞是具有运动性和侵袭性的体细胞，与卵巢癌细胞具有某些共同特征。通过对这种简单生物体的遗传学分析，已鉴定出许多调控边界细胞迁移时序和导向的蛋白质。
5. 基于黑腹果蝇的研究成果，一些哺乳动物蛋白（如肌球蛋白VI）的功能已被验证其调控卵巢癌细胞运动的能力。
6. 研究发现凋亡抑制蛋白除其众所周知的阻止细胞死亡功能外，还能促进边界细胞迁移，这揭示了细胞存活与运动性之间的内在联系。
7. 许多促进细胞运动的分子同时能增强对自然或化疗诱导的细胞死亡的抵抗力，这一发现为转移性疾病对治疗更具抵抗力的观察现象提供了可能的分子基础。

英文摘要：

Despite considerable efforts to improve early detection, and advances in chemotherapy, metastasis remains a major challenge in the clinical management of ovarian cancer. Studies of new murine models are providing novel insights into the pathophysiology of ovarian cancer, but these models are not readily amenable to genetic screens. Genetic analysis of border-cell migration in the Drosophila melanogaster ovary provides clues that will improve our understanding of ovarian cancer metastasis at the molecular level, and also might lead to potential therapeutic targets.

摘要翻译： 

尽管在早期检测和化疗方面已付出巨大努力，转移仍是卵巢癌临床管理中的主要难题。对小鼠新模型的研究正为卵巢癌的病理生理学提供新见解，但这些模型难以直接用于遗传学筛选。对果蝇卵巢边缘细胞迁移的遗传学分析，为在分子水平上理解卵巢癌转移提供了线索，并可能发现潜在的治疗靶点。

原文链接：

Ovarian Cancer Metastasis: Integrating insights from disparate model organisms