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Nuklearmedizin 1989; 28(06): 247-254
DOI: 10.1055/s-0038-1629498
Original Articles
Schattauer GmbH

Die Anämie bei malignen Tumorerkrankungen

II. Tumorbedingte Verluste von Transferrin als Ursache für die Entwicklung einer Anämie am Modell der RatteAnemia in Malignant DiseaseII. Tumor-Related Transferrin Loss as the Cause of Anemia in the Rat
E. Aulbert
1   Aus dem Ev. Waldkrankenhaus Spandau, BRD
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Publication History

Eingegangen: 05 December 1988

23 June 1989

Publication Date:
05 February 2018 (online)

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The cellular uptake and lysosomal accumulation of 67Ga-labelled transferrin within tumors of different malignancy were examined using tissue fractionation and immunological techniques. As tumor models the slowly growing Morris hepatoma 5123C, the moderately growing Novikoff hepatoma and the fast and aggressive Yoshida hepatoma AH 130 were investigated. Isolation of subcellular fractions of tumor homogenates was performed by differential centrifugation and density-gradient centrifugation. The intracellular 67Gatransferrin was found to be highly concentrated within the purified lysosomes. The transferrin within the lysosomal fraction was identified by radial immunodiffusion technique using monospecific antiserum. The accumulation of 67Gatransferrin by the tumors resulted in a faster disappearance of 67Ga-transferrin from the blood. This loss of circulating 67Ga-transferrin correlated with the proliferation activity and the spread of the tumors. Since transferrin is indispensible for the utilization of iron by the heme-synthesizing red cell precursors, transferrin concentration in the blood is the limiting factor for the utilization of iron in hemoglobin synthesis. Thus, in a further series of experiments we investigated the development of anemia in tumor-bearing rats. With increasing tumor mass a progressive fall of hemoglobin concentration was found. The anemia was more severe in the faster growing Novikoff hepatoma than in the slowly growing Morris hepatoma. The most significant reduction of hemoglobin concentration was found in the very fast growing Yoshida hepatoma. After total tumor resection hemoglobin concentration and red blood cell count normalized completely within 6-8 weeks. We conclude from these data that the uptake of transferrin by the tumor cells results in a faster disappearance of transferrin from the blood. This loss of circulating transferrin correlates with tumor mass and proliferation activity and is one of the factors responsible for the anemia seen in patients with malignant tumors.

Zusammenfassung

Es werden am Modell des langsam wachsenden Morris-Hepatoms 5123C, des mäßig schnell wachsenden Novi-koff-Hepatoms und des sehr schnell und aggressiv wachsenden Yoshida-Hepatoms AH 130 mit Hilfe der Differentialzentrifugation und der Dichtegradientenzentrifugation die subzellulären Fraktionen isoliert und die intrazelluläre Verteilung von 67Ga-markiertem Transferrin im Tumorgewebe untersucht. Es wird nachgewiesen, daß sich das 67Ga-Transferrin in den Lysosomen der Tumorzellen anreichert. Durch immunologische Methoden wird gezeigt, daß das Transferrin innerhalb der Lysosomen in immunologisch intakter Form vorliegt. Die Anreicherung von 67Ga-Transferrin im Tumorgewebe führt zu einer beschleunigten Elimination von zirkulierendem Transferrin aus dem Blut. Das Ausmaß dieser Transferrinverluste ist von der Größe und der Proliferationsaktivität der Tumoren abhängig. Es werden in einem zweiten Schritt die hämatologischen Parameter der tumortragenden Ratten untersucht. Dabei zeigt sich ein mit zunehmender Tumorgröße progredienter Abfall der Hämoglobinkonzentration im Blut. Dieser Abfall erfolgt desto steiler, je größer die Proliferationsaktivität der Tumoren ist. Da die Eisenzulieferung zur Hämoglobinsynthese von der Transferrinkonzentration im umgebenden Medium abhängt, wird aus den Befunden gefolgert, daß die tumorbedingten Transferrinverluste eine wesentliche Ursache für die Entstehung der »Tumoranämie« sind. Es wird gezeigt, daß nach Tumorrückbildung unter einer antineoplastischen Therapie eine völlige Normalisierung der Hämoglobinkonzentration im Blut der Tiere eintritt.

 

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