Kroeger M, Walenta S, Rofstad E K, Mueller-Klieser W
Institute of Physiology and Pathophysiology, University of Mainz, Germany.
Br J Cancer. 1995 Oct;72(4):912-6. doi: 10.1038/bjc.1995.432.
Investigations were carried out on two lines of human melanomas (MF; n = 12 and EE; n = 13) xenografted in nude mice. The tumours were characterised by a similar vascular supply but showed a pronounced difference in the rate of volume growth and in the radiobiologically hypoxic fraction. The distribution of ATP, glucose and lactate in the tumours was investigated using quantitative bioluminescence and single photon imaging. Concentrations of the metabolites were obtained as global values for the entire tumour mass, in regions with densely packed, structurally intact tumour cells ('viable zones'), in areas with necrosis, stromal cells and fibrous material ('necrotic zones') and in adjacent normal tissue. In all melanomas investigated glucose concentrations were significantly lower and lactate concentrations were significantly higher than in normal tissue. In contrast, no significant differences for ATP were detected. ATP and glucose concentrations were significantly less in necrotic than in viable tumour zones, whereas lactate concentrations were nearly equal in these tumour parts. Corresponding results were obtained in central versus peripheral tumour zones. There was no dependency of global or regional metabolite concentrations on tumour size within the volume range 110-1470 mm3. Based on this lack of dependency, metabolic concentrations were averaged over the whole tumour size range. Metabolite concentrations were not significantly different either globally or regionally between the two tumour entities investigated, a finding which held true for all three metabolites registered. Thus, metabolite distributions apparently mirror the similarity in vascularity of MF and EE melanomas rather than reflecting intrinsic properties with regard to tumour growth rates or susceptibility to radiation.
对移植于裸鼠体内的两株人黑色素瘤细胞系(MF,n = 12;EE,n = 13)进行了研究。这些肿瘤具有相似的血管供应,但在体积生长速率和放射生物学低氧分数方面存在显著差异。使用定量生物发光和单光子成像技术研究了肿瘤中三磷酸腺苷(ATP)、葡萄糖和乳酸的分布情况。获得了代谢物在整个肿瘤组织、肿瘤细胞密集且结构完整的区域(“存活区”)、存在坏死、基质细胞和纤维物质的区域(“坏死区”)以及相邻正常组织中的浓度,作为整个肿瘤块的总体值。在所研究的所有黑色素瘤中,葡萄糖浓度均显著低于正常组织,而乳酸浓度则显著高于正常组织。相比之下,未检测到ATP有显著差异。坏死肿瘤区域的ATP和葡萄糖浓度显著低于存活肿瘤区域,而这些肿瘤部位的乳酸浓度几乎相等。在肿瘤中央与外周区域也获得了相应结果。在110 - 1470立方毫米的体积范围内,总体或局部代谢物浓度与肿瘤大小无关。基于这种无关性,对整个肿瘤大小范围内的代谢浓度进行了平均。在所研究的两个肿瘤实体之间,总体或局部代谢物浓度均无显著差异,这一发现适用于所记录的所有三种代谢物。因此,代谢物分布显然反映了MF和EE黑色素瘤血管生成的相似性,而非反映肿瘤生长速率或对辐射敏感性的内在特性。