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Epidermal Growth Factor and Granulocyte Colony Stimulating Factor Signaling Are Synergistic for Hematopoietic Regeneration.

Publication ,  Journal Article
Piryani, SO; Kam, AYF; Kliassov, EG; Chen, BJ; Spector, NL; Chute, JP; Hsu, DS; Chao, NJ; Doan, PL
Published in: Stem Cells
February 2018

Hematopoietic regeneration following chemotherapy may be distinct from regeneration following radiation. While we have shown that epidermal growth factor (EGF) accelerates regeneration following radiation, its role following chemotherapy is currently unknown. We sought to identify EGF as a hematopoietic growth factor for chemotherapy-induced myelosuppression. Following 5-fluorouracil (5-FU), EGF accelerated hematopoietic stem cell regeneration and prolonged survival compared with saline-treated mice. To mitigate chemotherapy-induced injury to endothelial cells in vivo, we deleted Bax in VEcadherin+ cells (VEcadherinCre;BaxFL/FL mice). Following 5-FU, VEcadherinCre;BaxFL/FL mice displayed preserved hematopoietic stem/progenitor content compared with littermate controls. 5-FU and EGF treatment resulted in increased cellular proliferation, decreased apoptosis, and increased DNA double-strand break repair by non-homologous end-joining recombination compared with saline-treated control mice. When granulocyte colony stimulating factor (G-CSF) is given with EGF, this combination was synergistic for regeneration compared with either G-CSF or EGF alone. EGF increased G-CSF receptor (G-CSFR) expression following 5-FU. Conversely, G-CSF treatment increased both EGF receptor (EGFR) and phosphorylation of EGFR in hematopoietic stem/progenitor cells. In humans, the expression of EGFR is increased in patients with colorectal cancer treated with 5-FU compared with cancer patients not on 5-FU. Similarly, EGFR signaling is responsive to G-CSF in humans in vivo with both increased EGFR and phospho-EGFR in healthy human donors following G-CSF treatment compared with donors who did not receive G-CSF. These data identify EGF as a hematopoietic growth factor following myelosuppressive chemotherapy and that dual therapy with EGF and G-CSF may be an effective method to accelerate hematopoietic regeneration. Stem Cells 2018;36:252-264.

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Published In

Stem Cells

DOI

EISSN

1549-4918

Publication Date

February 2018

Volume

36

Issue

2

Start / End Page

252 / 264

Location

England

Related Subject Headings

  • Signal Transduction
  • Mice, Inbred C57BL
  • Mice
  • Immunology
  • Hematopoietic Stem Cells
  • Hematopoiesis
  • Granulocyte Colony-Stimulating Factor
  • Fluorouracil
  • ErbB Receptors
  • Epidermal Growth Factor
 

Citation

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Piryani, S. O., Kam, A. Y. F., Kliassov, E. G., Chen, B. J., Spector, N. L., Chute, J. P., … Doan, P. L. (2018). Epidermal Growth Factor and Granulocyte Colony Stimulating Factor Signaling Are Synergistic for Hematopoietic Regeneration. Stem Cells, 36(2), 252–264. https://doi.org/10.1002/stem.2731
Piryani, Sadhna O., Angel Y. F. Kam, Evelyna G. Kliassov, Benny J. Chen, Neil L. Spector, John P. Chute, David S. Hsu, Nelson J. Chao, and Phuong L. Doan. “Epidermal Growth Factor and Granulocyte Colony Stimulating Factor Signaling Are Synergistic for Hematopoietic Regeneration.Stem Cells 36, no. 2 (February 2018): 252–64. https://doi.org/10.1002/stem.2731.
Piryani SO, Kam AYF, Kliassov EG, Chen BJ, Spector NL, Chute JP, et al. Epidermal Growth Factor and Granulocyte Colony Stimulating Factor Signaling Are Synergistic for Hematopoietic Regeneration. Stem Cells. 2018 Feb;36(2):252–64.
Piryani, Sadhna O., et al. “Epidermal Growth Factor and Granulocyte Colony Stimulating Factor Signaling Are Synergistic for Hematopoietic Regeneration.Stem Cells, vol. 36, no. 2, Feb. 2018, pp. 252–64. Pubmed, doi:10.1002/stem.2731.
Piryani SO, Kam AYF, Kliassov EG, Chen BJ, Spector NL, Chute JP, Hsu DS, Chao NJ, Doan PL. Epidermal Growth Factor and Granulocyte Colony Stimulating Factor Signaling Are Synergistic for Hematopoietic Regeneration. Stem Cells. 2018 Feb;36(2):252–264.
Journal cover image

Published In

Stem Cells

DOI

EISSN

1549-4918

Publication Date

February 2018

Volume

36

Issue

2

Start / End Page

252 / 264

Location

England

Related Subject Headings

  • Signal Transduction
  • Mice, Inbred C57BL
  • Mice
  • Immunology
  • Hematopoietic Stem Cells
  • Hematopoiesis
  • Granulocyte Colony-Stimulating Factor
  • Fluorouracil
  • ErbB Receptors
  • Epidermal Growth Factor