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Generation of erythroid cells from polyploid giant cancer cells: re-thinking about tumor blood supply



During development and tumor progression, cells need a sufficient blood supply to maintain development and rapid growth. It is reported that there are three patterns of blood supply for tumor growth: endothelium-dependent vessels, mosaic vessels, and vasculogenic mimicry (VM). VM was first reported in highly aggressive uveal melanomas, with tumor cells mimicking the presence and function of endothelial cells forming the walls of VM vessels. The walls of mosaic vessels are randomly lined with both endothelial cells and tumor cells. We previously proposed a three-stage process, beginning with VM, progressing to mosaic vessels, and eventually leading to endothelium-dependent vessels. However, many phenomena unique to VM channel formation remain to be elucidated, such as the origin of erythrocytes before VM vessels connect with endothelium-dependent vessels.


In adults, erythroid cells are generally believed to be generated from hematopoietic stem cells in the bone marrow. In contrast, embryonic tissue obtains oxygen through formation of blood islands, which are largely composed of embryonic hemoglobin with a higher affinity with oxygen, in the absence of mature erythrocytes. Recent data from our laboratory suggest that embryonic blood-forming mechanisms also exist in cancer tissue, particularly when these tissues are under environmental stress such as hypoxia. We review the evidence from induced pluripotent stem cells in vitro and in vivo to support this previously underappreciated cell functionality in normal and cancer cells, including the ability to generate erythroid cells. We will also summarize the current understanding of tumor angiogenesis, VM, and our recent work on polyploid giant cancer cells, with emphasis on their ability to generate erythroid cells and their association with tumor growth under hypoxia.


An alternative embryonic pathway to obtain oxygen in cancer cells exists, particularly when they are under hypoxic conditions.

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Fig. 1



Polyploidy giant cancer cells

CoCl2 :

Cobalt chloride


Cancer stem cells


Vasculogenic mimicry

iPS cells:

Induced pluripotent stem cells


Mosaic vessels


Endothelium-dependent vessels


Mesenchymal stem cells


Hematopoietic stem cells




Embryonic stem cells


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This work was supported in part by Grants from the National Science Foundation of China (#81472729 and #81672426), the foundation of Tianjin Health Bureau (15KG112) and the foundation of committee on science and technology of Tianjin (17YFZCSY00700).

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Correspondence to Shiwu Zhang.

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Yang, Z., Yao, H., Fei, F. et al. Generation of erythroid cells from polyploid giant cancer cells: re-thinking about tumor blood supply. J Cancer Res Clin Oncol 144, 617–627 (2018). https://doi.org/10.1007/s00432-018-2598-4

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  • Erythropoiesis
  • Polyploidy giant cancer cells
  • Vasculogenic mimicry
  • Cancer stem cells