Das Tumormikromilieu

Summary

Solid malignant tumours are characterized by a heterogeneous metabolic micromilieu with the intra-individual variability within single tumours being substantially smaller than the inter-individual differences between tumours. Despite this variability, there are some hallmarks which are characteristic for the majority of malignancies. They include hypoxia, tissue acidosis, and abnormal microcirculation. Peculiarities of the carbohydrate metabolism and specifically of glycolysis in tumours receive increasing attention in experimental and clinical research.

As shown by our research with induced bioluminescence, different tumours from various entities exhibit a large spectrum of lactate accumulation. Interestingly, primary lesions with metastasis contain significantly higher amounts of lactate as compared to non-metastatic tumours. Classification into high and low lactate tumours according to the median lactate concentration in combination with a Kaplan-Meier analysis reveals that survival of patients with high lactate tumours is significantly worse than that with low lactate carcinomas. Furthermore, there is a positive correlation between tumour lactate content and radio-resistance. Conclusion: High lactate tumours are characterized by a higher degree of malignancy and therapeutic resistance.

Zusammenfassung

Solide maligne Tumoren haben ein sehr heterogenes metabolisches Mikromilieu, wobei die intra-individuelle Variabilität einzelner Tumoren meist wesentlich kleiner ist als die inter-individuellen Unterschiede verschiedener Malignome. Trotz dieser Variabilität lassen sich einige für Tumoren typische Merkmale feststellen, die in der Mehrzahl der Erkrankungen auftreten. Dazu zählen Hypoxie, Gewebe – azidose und abnormale Mikrozirkulation. Seit einigen Jahren finden die Besonderheiten des Kohlenhydratstoffwechsels in Tumoren und besonders die Tumorglykolyse in der experimentellen und klinischen Forschung wachsende Beachtung.

Wie eigene Untersuchungen mit induzierter Biolumineszenz ergaben, zeigen viele Tumoren aus unterschiedlichen Entitäten eine sehr variable Anreicherung von Laktat. Dabei enthalten bereits metastasierte Primärläsionen signifikant mehr Laktat als Tumoren ohne Metastasen. Eine Klassifikation nach dem medianen Laktatgehalt in Hoch- und Niedriglaktat-Tumoren sowie eine Kaplan-Meier-Überlebensanalyse zeigen, dass Patienten mit Hoch lakat-Tumoren eine signifikant niedrigere Überlebensrate aufweisen im Vergleich zu denen mit Niedriglaktat-Karzinomen. Die Anreicherung von Laktat in Tumoren ist außerdem positiv mit der Strahlenresistenz korreliert. Schlussfolgerung: Hochglykolytische, Laktat-akkumulierende Tumoren weisen einen hohen Malignitätsgrad und eine große Therapieresistenz auf.

Keywords

Micromilieu - glycolysis in tumours - lactate - radio-resistance

Schlüsselwörter

Tumormikromilieu - Tumorglykolyse - Laktat - Strahlenresistenz

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