| 摘要: |
| 肺癌的生长和转移都需要新生血管的支持,新生血管生成在肺癌的发生、发展中扮演关键角色。新生血管生成由肿瘤微环境所决定,多种信号分子共同参与其调控。肺癌新生血管生成的主要过程可归纳为:(1)肿瘤不断生长促使其微环境内部发生“血管生成转换”而启动促血管程序；(2)基质金属蛋白酶诱导细胞外基质(ECM)降解与重构；(3)内皮细胞在血小板源性生长因子和趋化因子的诱导下通过重构的ECM发生定向迁移；(4)在血管内皮细胞生长因子和成纤维细胞生长因子的作用下,内皮细胞大量增殖；(5)在Dll4-Notch通路的诱导下,最终形成血管管腔结构并具有完善的供血功能。目前,抑制血管生成已成为肺癌治疗的重要方向,新生血管生成全过程中的每个阶段均可能成为抑制肺癌的靶点。深入了解肺癌新生血管生成机制,对寻找有效的抗血管、抗肺癌治疗方法具有重要临床意义。 |
| 关键词: 肺肿瘤 血管生成 病理性新生血管化 信号通路 |
| DOI：10.3724/SP.J.1008.2013.00434 |
| 投稿时间：2012-11-16修订日期：2013-03-04 |
| 基金项目:国家自然科学基金(81172227),上海市教委科研资助项目 (12ZZ073). |
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| Mechanism of lung cancer angiogenesis: recent advance |
| YANG Meng-hang,ZANG Yuan-sheng,LI Bing* |
| (Department of Respiratory Medicine, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China) |
| Abstract: |
| Angiogenesis is essential for tumor growth and metastasis, and it plays a key role in the development and progression of lung cancer. Angiogenesis is determined by the tumor microenvironment and regulated by multiple signaling pathways. Lung cancer angiogenesis process can be summarized as follows: (1) Continuing growth of tumor promotes the so-called “angiogenic switch” in the microenvironment, starting the angiogenic process; (2) Matrix metalloproteinases (MMPs) induce the degradation and remodeling of extracellular matrix (ECM); (3) Endothelial cells migrate through the remodeled ECM as induced by platelet-derived growth factor (PDGF) and chemokines; (4) In presence of vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF), endothelial cells greatly proliferates; and (5) Lumen formation and vascular function are achieved by Dll4-Notch signaling. Currently, inhibition of angiogenesis has become an important option for lung cancer. Each stage of angiogenesis may become a potential target for treatment. New lights on the mechanisms of lung cancer angiogenesis is of great clinical significance for seaching effective anti-angiogenic and anti-lung cancer therapeutic methods. |
| Key words: lung neoplasms angiogenesis pathologic neovascularization signaling pathway |
