کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4496149 1623849 2014 14 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Glucose–lactate metabolic cooperation in cancer: Insights from a spatial mathematical model and implications for targeted therapy
ترجمه فارسی عنوان
همکاری متابولیک گلوکز در زمینه سرطان: بینش از یک مدل ریاضی فضایی و پیامدهای درمان هدفمند
کلمات کلیدی
متابولیسم سرطان، معادلات دیفرانسیل جزئی، تجزیه و تحلیل حساسیت چند بعدی
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک علوم کشاورزی و بیولوژیک (عمومی)
چکیده انگلیسی


• A recent controversial hypothesis proposed a metabolic cooperation in tumours.
• We develop a simple model to explore the hypothesis in a theoretical setting.
• Metabolic cooperation is found to be a robust feature of our model system.
• A treatment targeting the cooperation has only some of the expected effects.
• Experiments raise a new question of how cooperation might relate to malignancy.

A recent study has hypothesised a glucose–lactate metabolic symbiosis between adjacent hypoxic and oxygenated regions of a developing tumour, and proposed a treatment strategy to target this symbiosis. However, in vivo experimental support remains inconclusive. Here we develop a minimal spatial mathematical model of glucose–lactate metabolism to examine, in principle, whether metabolic symbiosis is plausible in human tumours, and to assess the potential impact of inhibiting it. We find that symbiosis is a robust feature of our model system—although on the length scale at which oxygen supply is diffusion-limited, its occurrence requires very high cellular metabolic activity—and that necrosis in the tumour core is reduced in the presence of symbiosis. Upon simulating therapeutic inhibition of lactate uptake, we predict that targeted treatment increases the extent of tissue oxygenation without increasing core necrosis. The oxygenation effect is correlated strongly with the extent of wild-type hypoxia and only weakly with wild-type symbiotic behaviour, and therefore may be promising for radiosensitisation of hypoxic, lactate-consuming tumours even if they do not exhibit a spatially well-defined symbiosis. Finally, we conduct in vitro experiments on the U87 glioblastoma cell line to facilitate preliminary speculation as to where highly malignant tumours might fall in our parameter space, and find that these experiments suggest a weakly symbiotic regime for U87 cells, thus raising the new question of what relationship might exist between symbiosis and tumour malignancy.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Theoretical Biology - Volume 361, 21 November 2014, Pages 190–203
نویسندگان
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