Tumors: wounds that do not heal-redux.
Tumors: wounds that do not heal-redux.
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DOI：
10.1158/2326-6066.cir-14-0209
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发表时间：
2015-01
影响因子：
10.1
通讯作者：
Dvorak HF
中科院分区：
文献类型：
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作者：
Dvorak HF
肿瘤和与伤口愈合相关的炎症反应之间的相似之处已经被认识了150多年，并继续引起人们的兴趣。几年前，基于我们最近发现的血管渗透因子(VPF)/血管内皮生长因子(VEGF)，我认为肿瘤表现为无法愈合的伤口。更具体地说，我提出，肿瘤辅助伤口愈合反应，以诱导它们维持和生长所需的基质。过去几十年的研究支持了这一假说，并将其建立在更坚实的分子基础上。总而言之，VPF/VEGF在肿瘤和伤口中启动了一系列事件，包括：血管通透性增加；血浆、纤维蛋白原和其他血浆蛋白的外渗；血管系统外凝血系统的激活；血管外纤维蛋白凝胶的沉积，作为临时基质和细胞迁移的有利基质；诱导血管生成和动静脉生成；随后纤维蛋白的降解并被“肉芽组织”(高度血管结缔组织)取代；最后，血管吸收和胶原合成，导致致密的纤维结缔组织的形成(在伤口中称为“疤痕组织”，在癌症中称为“结缔组织”)。在涉及细胞免疫的各种重要炎症性疾病中也会发生类似的事件序列。
Similarities between tumors and the inflammatory response associated with wound healing have been recognized for more than 150 years and continue to intrigue. Some years ago, based on our then recent discovery of vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF), I suggested that tumors behaved as wounds that do not heal. More particularly, I proposed that tumors co-opted the wound healing response in order to induce the stroma they required for maintenance and growth. Work over the past few decades has supported this hypothesis and has put it on a firmer molecular basis. In outline, VPF/VEGF initiates a sequence of events in both tumors and wounds that includes the following: increased vascular permeability; extravasation of plasma, fibrinogen and other plasma proteins; activation of the clotting system outside the vascular system; deposition of an extravascular fibrin gel which serves as a provisional stroma and a favorable matrix for cell migration; induction of angiogenesis and arterio-venogenesis; subsequent degradation of fibrin and its replacement by “granulation tissue” (highly vascular connective tissue); and, finally, vascular resorption and collagen synthesis, resulting in the formation of dense fibrous connective tissue (called “scar tissue” in wounds and “desmoplasia” in cancer). A similar sequence of events also takes place in a variety of important inflammatory diseases that involve cellular immunity.