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Fig. 1 | Inflammation and Regeneration

Fig. 1

From: Cancer ego-system in glioma: an iron-replenishing niche network systemically self-organized by cancer stem cells

Fig. 1

Systemic cancer ecosystem self-organized by CSCs in glioma-bearing mice. A functional niche network for CSCs to replenish iron, indispensable to GSC expansion themselves, is delineated by interconnecting GSC-induced TAM development in brain, and GSC-triggered enhanced erythropoiesis in peripheral. (1) Glioma: TfR+ GSCs recruit CCR2CD68inflammatory monocytes (iMo) from peripheral BM and induce F4/80CD163CD204+ tumor-associated macrophages (TAMs) through secreting some soluble factors such as CCL2 and CSF1/2 [Mo/Mφ development]. On the other hand, GSCs facilitate medullar and extramedullar erythropoiesis in peripheral hematopoietic organs, i.e., BM and spleen, potentially through secreting some soluble mediators. Collectively, Ter119+ hemorrhaged erythrocytes (hEC) infiltrating from peripheral are phagocytosed by the TAMs in brain and catabolized into iron [erythrophagocytosis and iron recycling]. Iron is stored in TAMs and potentially released upon the demands of GSCs highly expressing the receptor for the iron-carrier transferrin (Tf) [iron replenishment]. (2) Spleen: CD163TIM4+ red pulp macrophages (RPMs) originally have the ability to engulf the aged and damaged erythrocytes (a/dECs) externalizing phosphatidylserine (PS) at the cell surface to recycle and release iron into blood stream at the time of needs [erythrophagocytosis and iron recycling]. (3) Bone marrow (BM): hematopoietic differentiation from common myeloid progenitors (cMP) to erythroblasts (EB), reticulocytes (Retic), and erythrocytes (EC) is enhanced in glioma-bearing mouse BM [erythropoiesis], potentially maintaining the influx of erythrocytes hemorrhaged into glioma tissues. In BM erythropoiesis, CD169+ nurse macrophages uptake the recycling iron from blood stream and supply it for EBs to synthesize hemoglobin from heme composed of protoporphyrin IX (PpIX) and iron. Such heme synthesis pathway is also elevated in iron-demanding TfR+ GSCs, causing them to escape from 5-ALA-based photodynamic diagnosis (PDD) during surgical operation

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