title: Macrophages support splenic erythropoiesis in 4T1 tumor-bearing mice.
abstract: Anemia is a common complication of cancer; a role of spleen in tumor-stress erythropoiesis has been suggested. However, the molecular mechanisms involved in the splenic erythropoiesis following tumor maintenance remain poorly understood. Here we show that tumor development blocks medullar erythropoiesis by granulocyte colony-stimulating factor (G-CSF) and then causes anemia in murine 4T1 breast tumor-bearing mice. Meanwhile, tumor-stress promotes splenic erythropoiesis. Splenectomy worsened tumor-induced anemia, and reduced tumor volume and tumor weight, indicating the essential role of spleen in tumor-stress erythropoiesis and tumor growth. Tumor progression of these mice led to increased amounts of bone morphogenetic protein 4 (BMP4) in spleen. The in vivo role of macrophages in splenic erythropoiesis under tumor-stress conditions was investigated. Macrophage depletion by injecting liposomal clodronate decreased the expression of BMP4, inhibited splenic erythropoiesis, aggravated the tumor-induced anemia and suppressed tumor growth. Our results provide insight that macrophages and BMP4 are positive regulators of splenic erythropoiesis in tumor pathological situations. These findings reveal that during the tumor-stress period, the microenvironment of the spleen is undergoing changes, which contributes to adopt a stress erythropoietic fate and supports the expansion and differentiation of stress erythroid progenitors, thereby replenishing red blood cells and promoting tumor growth.
authors.affiliation: Department of Pharmacology, School of Medicine, Shandong University, Jinan, 250012, China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, School of Medicine, Shandong University, Jinan, 250012, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Jin
authors.affiliation: Qilu Hospital, Shandong University, Jinan, 250012, China.
authors.forename: Xigan
authors.initials: X
authors.lastname: He
authors.affiliation: Department of Pharmacology, School of Medicine, Shandong University, Jinan, 250012, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Pan
authors.affiliation: Department of Pharmacology, School of Medicine, Shandong University, Jinan, 250012, China.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, School of Medicine, Shandong University, Jinan, 250012, China.
authors.forename: Yunxue
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000740:Anemia / Q000097:blood / Q000209:etiology / Q000473:pathology; D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D004002:Clodronic Acid / Q000494:pharmacology; D018450:Disease Progression; D004920:Erythropoiesis; D004921:Erythropoietin / Q000096:biosynthesis; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood; D008264:Macrophages / Q000187:drug effects / Q000473:pathology*; D008325:Mammary Neoplasms, Experimental / Q000097:blood / Q000150:complications / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000473:pathology*; D013156:Splenectomy
chemical_list: C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D004002:Clodronic Acid; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor
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