Iron- and erythropoietin-resistant anemia in a spontaneous breast cancer mouse model.

Autor: Bregolat NF; Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland; Center for Clinical Studies, Vetsuisse Faculty, University of Zurich, Zurich., Ruetten M; PathoVet AG, Pathology Diagnostic Laboratory, Tagelswangen ZH., Da Silva MC; Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg., Aboouf MA; Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland; Center for Clinical Studies, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland; Departement of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo., Ademi H; Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland; Center for Clinical Studies, Vetsuisse Faculty, University of Zurich, Zurich., Büren NV; Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland; Center for Clinical Studies, Vetsuisse Faculty, University of Zurich, Zurich., Armbruster J; Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland; Center for Clinical Studies, Vetsuisse Faculty, University of Zurich, Zurich., Stirn M; Clinical Laboratory, Department of Clinical Diagnostics and Services, Vetsuisse Faculty, University of Zurich, Zurich., Altamura S; Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany; Molecular Medicine Partnership Unit, Heidelberg., Marques O; Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany; Molecular Medicine Partnership Unit, Heidelberg., Rodriguez JMM; Laboratory for Animal Model Pathology, Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, Zurich., Samillan VJ; Universidad Le Cordon Bleu, School of Human Nutrition, Lima., Singh RP; Institute of Clinical Chemistry and Laboratory Medicine, Carl Gustav Carus, TU Dresden., Wielockx B; Institute of Clinical Chemistry and Laboratory Medicine, Carl Gustav Carus, TU Dresden., Muckenthaler MU; Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Heidelberg, Germany; 7Molecular Medicine Partnership Unit, Heidelberg, Germany; Translational Lung Research Center Heidelberg (TLRC), German Center for Lung Research (DZL), University of Heidelberg, Germany; German Centre for Cardiovascular Research, Partner Site., Gassmann M; Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland; Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich., Thiersch M; Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland; Center for Clinical Studies, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland; Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich. markus.thiersch@uzh.ch.
Jazyk: angličtina
Zdroj: Haematologica [Haematologica] 2022 Oct 01; Vol. 107 (10), pp. 2454-2465. Date of Electronic Publication: 2022 Oct 01.
DOI: 10.3324/haematol.2022.280732
Abstrakt: Anemia of cancer (AoC) with its multifactorial etiology and complex pathology is a poor prognostic indicator for cancer patients. One of the main causes of AoC is cancer-associated inflammation that activates mechanisms, commonly observed in anemia of inflammation, whereby functional iron deficiency and iron-restricted erythropoiesis are induced by increased hepcidin levels in response to raised levels of interleukin-6. So far only a few AoC mouse models have been described, and most of them did not fully recapitulate the interplay of anemia, increased hepcidin levels and functional iron deficiency in human patients. To test if the selection and the complexity of AoC mouse models dictates the pathology or if AoC in mice per se develops independently of iron deficiency, we characterized AoC in Trp53floxWapCre mice that spontaneously develop breast cancer. These mice developed AoC associated with high levels of interleukin-6 and iron deficiency. However, hepcidin levels were not increased and hypoferremia coincided with anemia rather than causing it. Instead, an early shift in the commitment of common myeloid progenitors from the erythroid to the myeloid lineage resulted in increased myelopoiesis and in the excessive production of neutrophils that accumulate in necrotic tumor regions. This process could not be prevented by either iron or erythropoietin treatment. Trp53floxWapCre mice are the first mouse model in which erythropoietin-resistant anemia is described and may serve as a disease model to test therapeutic approaches for a subpopulation of human cancer patients with normal or corrected iron levels who do not respond to erythropoietin.
Databáze: MEDLINE