Blood flow, oxygenation, metabolic and energetic status in different clonal subpopulations of a rat rhabdomyosarcoma.

Abstract

Differentiation of a tumor plays an important role in terms of biological aggressiveness. The question arises as to whether this is reflected in differences in the metabolic and energetic status of solid tumors. The aim of this study was to analyze the influence of clonal tumor cell differentiation on the microenvironment of rat rhabdomyosarcomas. Two distinct lines of a rhabdomyosarcoma (BA-HAN-1) with different histomorphological properties were used (line F1, co-existence of mononuclear stellate cells and multinuclear myotube-like giant tumor cells; G8, polygonal, mononuclear tumor cells). Solid tumors were grown s.c. on the hind food dorsum of Lewis rats. Tumor oxygenation was measured using O2-sensitive needle electrodes. For determining tumor blood flow, the 133Xe clearance method was used. Global glucose and lactate concentrations were measured enzymatically, global ATP, ADP, and AMP were analyzed by HPLC. The regional distribution of metabolic and energetic parameters within the tumors was analyzed using quantitative bioluminescence and image analysis. Tumor growth rate was significantly different between the two lines. The volume doubling time was 2.5 days for the F1 and 3.0 days for G8 tumors. No differences in blood flow were seen between the two lines investigated, oxygenation was slightly poorer, glucose and ATP levels slightly higher, and lactate concentration somewhat lower in the F1 line as compared to the G8 line. From these differences - although marginal - it is concluded that the G8 line presumably relies on glycolysis whereas the F1 line seems to prefer oxidative glucose turnover. Despite these different metabolic profiles between the two tumor lines, the histopathology of the rhabdomyosarcomas seems to be only of limited significance for the tissue oxygenation status as already postulated for various tumors in the clinical setting.