文章：

血管生成和淋巴管生成中的整合素

Integrins in angiogenesis and lymphangiogenesis

原文发布日期：2008-05-22

DOI: 10.1038/nrc2353

类型: Review Article

开放获取: 否

要点：

1. Angiogenesis and lymphangiogenesis have important roles in cancer progression: angiogenesis, the growth of new blood vessels, promotes tumour growth and tumour metastasis, and lymphangiogenesis, the growth of new lymphatic vessels, promotes tumour metastasis. Angiogenesis and lymphangiogenesis are regulated by integrins, which are members of a family of cell surface adhesion receptors.
2. The integrin family is an extensive group of structurally related receptors for extracellular matrix proteins and immunoglobulin superfamily molecules. Integrin ligation promotes intracellular signal transduction, cell migration and survival in angiogenesis and lymphangiogenesis.
3. A number of endothelial cell integrins regulate angiogenesis in diverse manners, including integrins α1β1, α2β1, α4β1, α5β1, α9β1 and α6β4. αv integrins are also important in angiogenesis, although the exact nature of these roles is hotly disputed. Expression and function analysis of αv integrins in wild-type animals using integrin antagonists as well as analysis of knock-in mutant mice indicate that αv integrins promote angiogenesis, whereas genetic deletion studies suggest that αv integrins are not required for angiogenesis.
4. Although less is known about the integrins that regulate lymphangiogenesis, integrin α9 is required for normal developmental lymphangiogenesis. Integrins α4β1, α2β1 and α1β1 have also been implicated in the regulation of tumour lymphangiogenesis.
5. Integrins on bone marrow-derived myeloid cells can also promote angiogenesis. Circulating bone marrow-derived cells migrate into tumours in response to tumour-secreted chemokines and cytokines and integrins α4β1 and αMβ2 (CD11b) have key roles in this process, indirectly influencing tumour angiogenesis.
6. Antagonists of several integrins, including αvβ3, αvβ5 and α5β1, are currently under investigation as clinical agents to suppress tumour angiogenesis and growth either alone or in combination with current cancer therapeutics.

要点翻译：

1. 血管生成和淋巴管生成在癌症进展中具有重要作用：血管生成，即新血管的生长，促进肿瘤生长和肿瘤转移；而淋巴管生成，即新淋巴管的生长，促进肿瘤转移。血管生成和淋巴管生成受整合素调控，整合素是细胞表面黏附受体家族的成员。
2. 整合素家族是一个广泛的结构相关受体群，作用于细胞外基质蛋白和免疫球蛋白超家族分子。整合素连接促进细胞内信号转导、细胞迁移以及在血管生成和淋巴管生成中的细胞存活。
3. 多种内皮细胞整合素以不同方式调控血管生成，包括整合素α1β1、α2β1、α4β1、α5β1、α9β1和α6β4。αv整合素在血管生成中也十分重要，尽管这些作用的具体性质存在激烈争议。在野生型动物中使用整合素拮抗剂对αv整合素进行表达和功能分析，以及对敲入突变小鼠的分析表明，αv整合素促进血管生成，而基因缺失研究则提示αv整合素在血管生成中并非必需。
4. 尽管对调控淋巴管生成的整合素了解较少，但整合素α9是正常发育淋巴管生成所必需的。整合素α4β1、α2β1和α1β1也被认为与肿瘤淋巴管生成的调控有关。
5. 骨髓来源的髓系细胞上的整合素也能促进血管生成。循环的骨髓来源细胞响应肿瘤分泌的趋化因子和细胞因子迁移至肿瘤内部，而整合素α4β1和αMβ2（CD11b）在此过程中起关键作用，间接影响肿瘤血管生成。
6. 数种整合素的拮抗剂，包括αvβ3、αvβ5和α5β1，目前正在作为临床药物进行研究，旨在单独或与现有癌症疗法联合使用以抑制肿瘤血管生成和生长。

英文摘要：

Blood vessels promote tumour growth, and both blood and lymphatic vessels facilitate tumour metastasis by serving as conduits for the transport of tumour cells to new sites. Angiogenesis and lymphangiogenesis are regulated by integrins, which are members of a family of cell surface receptors whose ligands are extracellular matrix proteins and immunoglobulin superfamily molecules. Select integrins promote endothelial cell migration and survival during angiogenesis and lymphangiogenesis, whereas other integrins promote pro-angiogenic macrophage trafficking to tumours. Several integrin-targeted therapeutic agents are currently in clinical trials for cancer therapy. Here, we review the evidence implicating integrins as a family of fundamental regulators of angiogenesis and lymphangiogenesis.

摘要翻译： 

血管促进肿瘤生长，血液和淋巴管通过作为将肿瘤细胞运输到新部位的通道来促进肿瘤转移。血管生成和淋巴管生成受到整合素的调控，整合素是一类细胞表面受体家族，其配体为细胞外基质蛋白和免疫球蛋白超家族分子。某些整合素在血管生成和淋巴管生成过程中促进内皮细胞的迁移和存活，而其他整合素则促进促血管生成的巨噬细胞向肿瘤迁移。几种靶向整合素的治疗药物目前正在癌症治疗的临床试验中。在此，我们回顾了整合素作为血管生成和淋巴管生成基本调控因子家族的证据。

原文链接：

Integrins in angiogenesis and lymphangiogenesis