肿瘤: 是不愈合的伤口

Tumors: Wounds That Do Not Heal—Redux

Harold F. Dvorak

文摘

肿瘤与创伤愈合相关的炎症反应的相似性已经被确认了150多年，并继续引起人们的兴趣。

几年前，根据我们最近发现的血管通透性因子(VPF)/VEGF，我认为肿瘤表现为不愈合的伤口。

更特别的是，我认为肿瘤选择伤口愈合的反应来诱导它们需要的基质来维持和生长。

过去几十年的工作支持了这一假设，并将其置于更为坚实的分子基础之上。

在概述中，VPF/VEGF在肿瘤和伤口中启动一系列事件，其中包括:增加血管通透性;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;一种血管外纤维蛋白凝胶的沉积，作为一种临时基质，是细胞迁移的有利基质;诱导血管生成和动静脉发生;纤维蛋白的降解及其替代的“肉芽组织”(高血管结缔组织);最后，血管再吸收和胶原合成，形成致密纤维结缔组织(在伤口中称为“疤痕组织”，在癌症中称为“desmoplasia”)。

　

类似的一系列事件也发生在涉及细胞免疫的各种重要炎症性疾病中。癌症Immunol Res;3(1);1 - 11。AACR©2015。

根据统计，大约10%左右的胃溃疡可发生癌变 。

参考文献：

Tumors: Wounds That Do Not Heal—Redux

Harold F. Dvorak

DOI: 10.1158/2326-6066.CIR-14-0209 Published January 2015

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Abstract

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)/VEGF, I suggested that tumors behaved as wounds that do not heal. More particularly, I proposed that tumors co-opted the wound-healing response 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 that 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. Cancer Immunol Res; 3(1); 1–11. ©2015 AACR.

Tumors: Wounds That Do Not Heal—Redux | Cancer Immunology Research  http://cancerimmunolres.aacrjournals.org/content/3/1/1