Oxygenation of human tumors: the Mainz experience

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.