源于Ⅳ型胶原的肿瘤血管生成抑制剂

新血管生成是各种生理和病理过程发生的基础。在胚胎形成和胎盘发育等正常生理过程中，新血管的生成是至关重要的；然而对于一些疾病的产生，特别是肿瘤的生长、进展和转移，同样离不开血管生成的作用。伴随着“抗肿瘤血管生成疗法”的提出，控制血管生成“开关”的血管生成刺激因子和抑制因子成为研究的热点。Arresten、Canstatin、Tumstatin和Hexastatin是近些年发现的内源性的血管生成抑制因子，它们同系Ⅳ型胶原α链的非胶原区NC1，具有相似的结构和分子量大小，现有研究表明，它们能与内皮细胞表面整合素受体相结合，有效地抑制内皮细胞的增殖和迁移，降低肿瘤组织的微血管密度，切断肿瘤的营养和氧气供给，从而抑制肿瘤的生长和转移。对其作用机制的研究，将有助于肿瘤血管生成抑制剂新药的研发。

Type Ⅳ Collagen-derived Angiogenesis Inhibitors

New blood vessel growth via angiogenesis is a fundational process in both physiological and pathological conditions. Physiological angiogenesis is critical during embryogenesis and placental development, whereas pathological angiogenesis plays an important role in the progression of many disease, most notably tumor growth, progression and metastasis. As “antiangiogenesis therapy for tumor” was proposed, concentrated efforts was leading to the discovery of a growing number of pro- and anti- angiogenic molecules, both of which regulated the “angiogenic-switch”. Arresten, Canstatin, Tumstatin and Hexastatin are newly discovered endogenous angiogenesis inhibitors, which derive from non-collagenous(NC1) domain of the α chain of type Ⅳ collagen. They are similar in structure and molecular weight. Furthermore all of them have been shown as novel integrin ligands and exhibit an ability to inhibit endothelial cell proliferation and migration and lower the density of tumor microvessel. Tumor growth and metastasis are halted for lack of nutrients and oxygen supply. Advances in the understanding of their molecular mechanism may contribute to the discovery of kinds of pharmaceutical agents.