Tumor microenvironment abnormalities: Causes, consequences, and strategies to normalize
Tumor microenvironment abnormalities: Causes, consequences, and strategies to normalize
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DOI：
10.1002/jcb.21187
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发表时间：
2007-07-01
影响因子：
4
通讯作者：
Jain, Rakesh K.
中科院分区：
文献类型：
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作者：
Fukumura, Dai;Jain, Rakesh K.
实体瘤是由肿瘤细胞和嵌入细胞外基质中的未转化宿主基质细胞组成的器官样实体。各种基因的表达受到这些细胞、周围基质及其局部物理和生化微环境之间相互作用的影响。这些基因编码的产物反过来控制肿瘤的病理生理特征，引起肿瘤血管组织、结构和功能的异常。这些异常导致血流、血管通透性和微环境不均匀。增殖的肿瘤细胞产生固体应力，压迫血管和淋巴管。由于血管渗漏和功能性淋巴管缺乏，实体瘤中的间质液压力显着升高。这些异常中的每一种都形成了向肿瘤递送治疗剂的生理屏障。此外，肿瘤内的缺氧和酸中毒等代谢微环境阻碍了放射治疗和化疗等抗肿瘤治疗的疗效。明智地应用抗血管生成疗法有可能通过使肿瘤血管正常化并使它们更有效地输送氧气和药物来克服这些问题。抗血管生成和常规疗法的联合治疗在临床上显示出了希望。
A solid tumor is an organ-like entity comprised of neoplastic cells and non-transformed host stromal cells embedded in an extracellular matrix. The expression of various genes is influenced by interactions among these cells, surrounding matrix, and their local physical and biochemical microenvironment. The products encoded by these genes, in turn, control the pathophysiological characteristics of the tumor, and give rise to the abnormal organization, structure, and function of tumor blood vessels. These abnormalities contribute to heterogeneous blood flow, vascular permeability, and microenvironment. Proliferating tumor cells produce solid stress which compresses blood and lymphatic vessels. As a result of vessel leakiness and lack of functional lymphatics, interstitial fluid pressure is significantly elevated in solid tumors. Each of these abnormalities forms a physiological barrier to the delivery of therapeutic agents to tumors. Furthermore, the metabolic microenvironment in tumors such as hypoxia and acidosis hinder the efficacy of anti-tumor treatments such as radiation therapy and chemotherapy. A judicious application of anti-angiogenic therapy has the potential to overcome these problems by normalizing the tumor vessels and making them more efficient for delivery of oxygen and drugs. Combined anti-angiogenic and conventional therapies have shown promise in the clinic.