Biological response of multicellular emt6 spheroids to exogenous lactate

✍ Scribed by B. Bourrat-Floeck; K. Groebe; W. Mueller-Klieser

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: French
• Weight: 908 KB
• Volume: 47
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910470528

✦ Synopsis

The influence of elevated lactate concentrations, as found in tumor microregions, on cellular growth, viability, and metabolic state was studied employing the multicellular spheroid model. Spheroids of EMT6/Ro cells were cultured at 37°C in 5% or 20% (v/v) oxygen, using stirred media with various concentrations of exogenous lactate ranging from 0.0 mn (standard conditions) to 20.0 mM. Elevated concentrations of exogenous lactate led to a considerable decrease of the maximum spheroid diameter at growth saturation, e.g., for 20% 0, from around I700 p m to 700 p m in 0.0 and 20.0 mn lactate respectively. Histological investigations showed that the thickness of the viable cell rim was increased by elevated lactate concentrations in 20% 0,, whereas this correlation was reversed in 5% 0,. Cultivation of spheroids in increasing lactate concentrations was associated with a shift of metabolic pathways from net production to increased utilization of lactate in both 20% and 5% 0,, as determined by standard enzymatic assays. Oxygen tension (PO,) values measured with micro-electrodes were less in spheroids cultured in high lactate (9.0 and 20.0 mw) than under standard conditions, irrespective of the external oxygen concentration. This finding reflected a substantial increase in the cellular 0, consumption with elevated external lactate levels. A t given lactate concentrations, respiration rates that were derived from measured PO, distributions by theoretical considerations were significantly lower in 5% 0, than in 20% 0,.