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Updated: Aug 1, 2025
11:50
Ex vivo Mimicry of Normal and Abnormal Human Hematopoiesis
Published on: April 10, 2012
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Perivascular localized cells commit erythropoiesis in PDGF-B-expressing solid tumors.
Kayoko Hosaka1, Chenchen Wang2,3, Shiyue Zhang2,3
1Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden.
Cancer Communications (London, England)
|April 30, 2023
Summary
Tumor pericytes can differentiate into red blood cells (RBCs) and contribute to hematopoiesis. This discovery offers a new therapeutic strategy for targeting tumor growth and improving cancer treatment.
Area of Science:
- Hematology
- Oncology
- Cell Biology
Background:
- Tumors require a constant oxygen supply, primarily from red blood cells (RBCs).
- While bone marrow (BM) is the primary site of hematopoiesis, extramedullary hematopoiesis can occur in pathological conditions.
- The role of tumors in hematopoiesis and the potential of perivascular cells within the tumor microenvironment (TME) to contribute to this process remain largely unexplored.
Purpose of the Study:
- To investigate whether perivascular cells within tumors can differentiate into hematopoietic cells, specifically RBCs.
- To elucidate the mechanisms by which tumor pericytes might influence hematopoiesis within the TME.
Main Methods:
- Genome-wide expression profiling of mouse pericytes.
- In vivo genetic tracing using NG2-CreERT2:R26R-tdTomato mice.
- Fluorescence-activated cell sorting (FACS), single-cell sequencing, and colony formation assays.
- Quantitative polymerase chain reaction (qPCR), ELISA, and immunohistochemistry to assess erythropoietin (EPO) production.
- BM transplantation mouse models to study tumor erythropoiesis.
Main Results:
- Platelet-derived growth factor B (PDGF-B) stimulation induced NG2+ perivascular cells to exhibit hematopoietic stem and progenitor-like features, differentiating into the erythroid lineage.
- PDGF-B also stimulated cancer-associated fibroblasts to produce EPO, a key hormone for erythropoiesis.
- Genetic tracing confirmed a subpopulation of hematopoietic cells derived from perivascular cells within tumors.
- NG2+ cells from tumors acted as distinct erythroblast progenitor cells upon PDGF-B stimulation, differing from canonical BM hematopoietic stem cells.
Conclusions:
- Tumor tissues can harbor a novel form of hematopoiesis originating from perivascular cells.
- Perivascular cells in the TME can differentiate into erythroid cells, offering new insights into tumor biology.
- Targeting tumor-specific hematopoiesis presents a potential novel therapeutic strategy for cancer treatment.
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