Papetti Michael, Herman Ira M
Department of Cellular and Molecular Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Am J Physiol Cell Physiol. 2002 May;282(5):C947-70. doi: 10.1152/ajpcell.00389.2001.
Often those diseases most evasive to therapeutic intervention usurp the human body's own cellular machinery or deregulate normal physiological processes for propagation. Tumor-induced angiogenesis is a pathological condition that results from aberrant deployment of normal angiogenesis, an essential process in which the vascular tree is remodeled by the growth of new capillaries from preexisting vessels. Normal angiogenesis ensures that developing or healing tissues receive an adequate supply of nutrients. Within the confines of a tumor, the availability of nutrients is limited by competition among actively proliferating cells, and diffusion of metabolites is impeded by high interstitial pressure (Jain RK. Cancer Res 47: 3039-3051, 1987). As a result, tumor cells induce the formation of a new blood supply from the preexisting vasculature, and this affords tumor cells the ability to survive and propagate in a hostile environment. Because both normal and tumor-induced neovascularization fulfill the essential role of satisfying the metabolic demands of a tissue, the mechanisms by which cancer cells stimulate pathological neovascularization mimic those utilized by normal cells to foster physiological angiogenesis. This review investigates mechanisms of tumor-induced angiogenesis. The strategies used by cancer cells to develop their own blood supply are discussed in relation to those employed by normal cells during physiological angiogenesis. With an understanding of blood vessel growth in both normal and abnormal settings, we are better suited to design effective therapeutics for cancer.
通常，那些最难通过治疗干预治愈的疾病会利用人体自身的细胞机制，或破坏正常的生理过程以实现增殖。肿瘤诱导的血管生成是一种病理状态，它源于正常血管生成的异常发生，正常血管生成是一个重要过程，在此过程中，血管树通过从现有血管生长出新的毛细血管而进行重塑。正常的血管生成为发育中的组织或正在愈合的组织提供充足的营养供应。在肿瘤范围内，营养物质的可获得性受到活跃增殖细胞之间竞争的限制，代谢产物的扩散也因高组织间隙压力而受阻（Jain RK.《癌症研究》47: 3039 - 3051, 1987）。因此，肿瘤细胞诱导从现有脉管系统形成新的血液供应，这使肿瘤细胞能够在恶劣环境中存活和增殖。由于正常血管生成和肿瘤诱导的新血管生成都起着满足组织代谢需求的关键作用，癌细胞刺激病理性新血管生成的机制类似于正常细胞促进生理性血管生成所利用 的机制。本综述研究肿瘤诱导血管生成的机制。将癌细胞用于建立自身血液供应的策略与正常细胞在生理性血管生成过程中所采用的策略进行了讨论。了解正常和异常情况下的血管生长情况后，我们就能更好地设计出有效的癌症治疗方法。
