Vaupel P, Thews O, Kelleher D K, Hoeckel M
Institute of Physiology & Pathophysiology, University of Mainz, Germany.
Strahlenther Onkol. 1998 Dec;174 Suppl 4:6-12.
Tumor oxygenation is dependent on the cellular O2 consumption rate and on the O2 supply to the respiring cells. The latter is mainly determined by the convective transport via the blood and by the diffusional flux from the microvessels to the O2 consuming sites. Peculiarities of tumor tissue oxygenation can therefore mainly be attributed to characteristic structural and functional abnormalities of the tumor microcirculation (perfusion-limited O2 delivery), to a deterioration of the diffusion geometry (diffusion-limited O2 delivery), and--in some cases--to a reduced O2-carrying capacity of the blood due to tumor-associated anemia. As a result of a compromised and anisotropic microcirculation, the O2 availability to the cancer cells shows great variability, and many human malignancies reveal hypoxic tissue areas which are heterogeneously distributed within the tumor mass and which may be located next to well-perfused tumor areas (intra-tumor heterogeneity). As a rule, in most solid malignancies the tissue O2 status is poorer than in normal tissue at the site of tumor growth. Hypoxia in human tumors per se has been shown to contribute to resistance to standard radiotherapy, chemotherapy and photodynamic therapy with photosensitizing hematoporphyrins. In addition to conferring a direct resistance, hypoxia-induced inhibition of proliferation may also contribute to resistance since both modalities are primarily effective against rapidly dividing cells. Hypoxia in solid tumors, however, has further implications in the clinical setting: Recent data provide strong evidence suggesting that O2 deprived tumor cells are predisposed to a more malignant phenotype, i.e., tumor cells are more likely to be more metastatic and/or invasive. In addition, clonal heterogeneity is more pronounced in hypoxic tumors.
肿瘤氧合作用取决于细胞的氧气消耗率以及向进行呼吸作用的细胞的氧气供应。后者主要由通过血液的对流运输以及从微血管到氧气消耗部位的扩散通量决定。因此，肿瘤组织氧合作用的特殊性主要可归因于肿瘤微循环的特征性结构和功能异常（灌注受限的氧气输送）、扩散几何结构的恶化（扩散受限的氧气输送），以及在某些情况下，由于肿瘤相关性贫血导致血液携氧能力降低。由于微循环受损且呈各向异性，癌细胞获得氧气的情况差异很大，许多人类恶性肿瘤都显示出缺氧组织区域，这些区域在肿瘤块内分布不均，可能紧邻灌注良好的肿瘤区域（肿瘤内异质性）。通常，在大多数实体恶性肿瘤中，肿瘤生长部位的组织氧状态比正常组织差。已证明人类肿瘤中的缺氧本身会导致对标准放疗、化疗以及使用光敏血卟啉的光动力疗法产生抗性。除了赋予直接抗性外，缺氧诱导的增殖抑制也可能导致抗性，因为这两种治疗方式主要对快速分裂的细胞有效。然而，实体肿瘤中的缺氧在临床环境中还有其他影响：最近的数据提供了强有力的证据表明，缺氧的肿瘤细胞更容易呈现更恶性的表型，即肿瘤细胞更有可能具有更高的转移性和/或侵袭性。此外，缺氧肿瘤中的克隆异质性更为明显。
