Radiation Biology and Tumor Physiology Group, Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway.
Int J Radiat Oncol Biol Phys. 2012 Jul 15;83(4):1317-23. doi: 10.1016/j.ijrobp.2011.09.037. Epub 2012 Jan 21.
Blood perfusion in tumors is spatially and temporally heterogeneous, resulting in local fluctuations in tissue oxygen tension (pO(2)) and tissue regions showing cycling hypoxia. In this study, we investigated whether the pO(2) fluctuation pattern and the extent of cycling hypoxia differ between tumor types showing high (e.g., cervical carcinoma xenograft) and low (e.g., melanoma xenograft) fractions of connective tissue-associated blood vessels.
Two cervical carcinoma lines (CK-160 and TS-415) and two melanoma lines (A-07 and R-18) transplanted into BALB/c nu/nu mice were included in the study. Tissue pO(2) was measured simultaneously in two positions in each tumor by using a two-channel OxyLite fiber-optic oxygen-sensing device. The extent of acute and chronic hypoxia was assessed by combining a radiobiological and a pimonidazole-based immunohistochemical assay of tumor hypoxia.
The proportion of tumor regions showing pO(2) fluctuations, the pO(2) fluctuation frequency in these regions, and the relative amplitude of the pO(2) fluctuations were significantly higher in the melanoma xenografts than in the cervical carcinoma xenografts. Cervical carcinoma and melanoma xenografts did not differ significantly in the fraction of acutely hypoxic cells or the fraction of chronically hypoxic cells. However, the ratio between fraction of acutely hypoxic cells and fraction of chronically hypoxic cells was significantly higher in melanoma than in cervical carcinoma xenografts.
Temporal heterogeneity in blood flow and tissue pO(2) in tumors may depend on tumor histology. Connective tissue surrounding microvessels may stabilize blood flow and pO(2) and, thus, protect tumor tissue from cycling hypoxia.
肿瘤中的血液灌注在空间和时间上存在异质性，导致组织氧张力（pO(2)）出现局部波动，并出现组织周期性缺氧。本研究旨在探讨组织氧张力波动模式和周期性缺氧程度是否因具有高（如宫颈癌异种移植）和低（如黑色素瘤异种移植）结缔组织相关血管比例的肿瘤类型而有所不同。
将两种宫颈癌系（CK-160 和 TS-415）和两种黑色素瘤系（A-07 和 R-18）移植到 BALB/c nu/nu 小鼠中，纳入本研究。使用双通道 OxyLite 光纤氧敏探头同时测量每个肿瘤两个部位的组织 pO(2)。通过联合放射生物学和肿瘤缺氧的 pimonidazole 免疫组化检测评估急性和慢性缺氧的程度。
与宫颈癌异种移植相比，黑色素瘤异种移植中出现 pO(2)波动的肿瘤区域比例、这些区域的 pO(2)波动频率以及 pO(2)波动的相对幅度显著更高。宫颈癌和黑色素瘤异种移植在急性缺氧细胞比例或慢性缺氧细胞比例方面无显著差异。然而，急性缺氧细胞比例与慢性缺氧细胞比例之间的比值在黑色素瘤中显著高于宫颈癌异种移植。
肿瘤中血流和组织 pO(2)的时间异质性可能取决于肿瘤组织学。微血管周围的结缔组织可能会稳定血流和 pO(2)，从而保护肿瘤组织免受周期性缺氧的影响。
