文章：

Caveolae：挖掘小洞穴寻找新的癌症靶点

Caveolae: mining little caves for new cancer targets

原文发布日期：2003-08-01

DOI: 10.1038/nrc1146

类型: Review Article

开放获取: 否

要点：

1. Caveolae are dynamic, detergent-resistant microdomains that are enriched in cholesterol and glycosphingolipids. They have a distinct invaginated form that is easily detected by electron microscopy.
2. Caveolae constitute an alternative endocytic pathway to clathrin-coated pits.
3. Caveolae can mediate transcytosis — the transcellular movement of molecules (such as select blood-borne macromolecules) across the endothelial cell.
4. Caveolae contain signalling molecules, such as select heterotrimeric G proteins, non-receptor tyrosine kinases and endothelial nitric oxide synthase (eNOS), and seem to act as organized transducing centres that concentrate key signalling molecules.
5. Angiogenesis depends on nitric oxide produced by eNOS, which is concentrated at the endothelial-cell surface in caveolae. Caveola and its caveolins could be targeted to prevent angiogenesis through inhibition of eNOS.
6. Caveolin seems to act as a tumour suppressor in cultured cells, but might be required for later stages of tumour development in vivo, when it promotes cancer-cell survival, metastasis and chemoresistance.
7. Caveolae with their tissue-specific molecules constitute a trafficking pathway that might be worth targeting — not only for site-directed drug and gene delivery but also to overcome the normally restrictive endothelial-cell barrier to reach underlying tissue or tumour cells.
8. Strategies to target caveolae, and even caveolin-1, might be useful in treating cancer through vascular ablation or functional disruption of metastasis, tumorigenesis, angiogenesis and tumour progression.

要点翻译：

1. 小窝是动态的、抗去污剂的微区，富含胆固醇和糖鞘脂。它们具有独特的凹陷形态，易于通过电子显微镜检测。
2. 小窝构成了网格蛋白包被小窝之外的另一种内吞途径。
3. 小窝可介导转胞吞作用——即分子（如特定的血源性大分子）跨内皮细胞的穿细胞运动。
4. 小窝含有信号分子，如特定的异源三聚体G蛋白、非受体酪氨酸激酶和内皮型一氧化氮合酶（eNOS），似乎充当着浓缩关键信号分子的有序转导中心。
5. 血管生成依赖于eNOS产生的一氧化氮，该酶集中存在于小窝的内皮细胞表面。小窝及其小窝蛋白可作为靶点，通过抑制eNOS来阻止血管生成。
6. 在培养细胞中，小窝蛋白似乎起到肿瘤抑制因子的作用，但在体内肿瘤发展的后期阶段，当它促进癌细胞存活、转移和化疗耐药时，可能是必需的。
7. 具有组织特异性分子的小窝构成了一种运输途径，可能值得作为靶点——不仅用于定点药物和基因递送，还可用于突破通常具有限制性的内皮细胞屏障，以到达下层组织或肿瘤细胞。
8. 靶向小窝甚至小窝蛋白-1的策略，可能通过血管消融或功能性地破坏转移、肿瘤发生、血管生成和肿瘤进展，对治疗癌症有用。

英文摘要：

Caveolae exist at cell surfaces as caveolin-coated invaginations that perform transport and signalling functions influencing cell growth, apoptosis, angiogenesis and transvascular exchange. Caveolin could constitute a key switch in tumour development through its function as a tumour suppressor and as a promoter of metastasis, chemoresistance and survival. Targeting of drugs and gene vectors to tissue-specific proteins in caveolae allows selective delivery into vascular endothelial cells in vivo and might even improve direct access to solid-tumour cells. Therefore, caveolae seem to be rich in potential targets for cancer imaging and therapeutics.

摘要翻译： 

小窝（Caveolae）是细胞表面由小窝蛋白（caveolin）包被的内陷结构，具有运输和信号传导功能，可影响细胞生长、凋亡、血管生成及跨血管交换。小窝蛋白通过其作为肿瘤抑制因子和促进转移、化疗耐药及细胞存活的双重作用，可能成为肿瘤发展的关键开关。将药物和基因载体靶向组织特异性小窝蛋白，可实现体内选择性递送至血管内皮细胞，甚至有望提高对实体瘤细胞的直接作用。因此，小窝在癌症成像和治疗中似乎富含潜在靶点。

原文链接：

Caveolae: mining little caves for new cancer targets