Sinusoidal ephrin receptor EPHB4 controls hematopoietic progenitor cell mobilization from bone marrow

Hyeongil Kwak, Ombretta Salvucci, Roberto Weigert, Jorge L. Martinez-Torrecuadrada, Mark Henkemeyer, Michael G. Poulos, Jason M. Butler, Giovanna Tosato

Research output: Contribution to journalArticle

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Abstract

Hematopoietic stem and progenitor cells (HSPCs) reside in the bone marrow. Stress signals from cancer and other conditions promote HSPC mobilization into circulation and subsequent homing to tissue microenvironments. HSPC infiltration into tissue microenvironments can influence disease progression; notably, in cancer, HSPCs encourage tumor growth. Here we have uncovered a mutually exclusive distribution of EPHB4 receptors in bone marrow sinusoids and ephrin B2 ligands in hematopoietic cells. We determined that signaling interactions between EPHB4 and ephrin B2 control HSPC mobilization from the bone marrow. In mice, blockade of the EPHB4/ephrin B2 signaling pathway reduced mobilization of HSPCs and other myeloid cells to the circulation. EPHB4/ephrin B2 blockade also reduced HSPC infiltration into tumors as well as tumor progression in murine models of melanoma and mammary cancer. These results identify EPHB4/ephrin B2 signaling as critical to HSPC mobilization from bone marrow and provide a potential strategy for reducing cancer progression by targeting the bone marrow.

Original languageEnglish (US)
Pages (from-to)4554-4568
Number of pages15
JournalJournal of Clinical Investigation
Volume126
Issue number12
DOIs
StatePublished - Dec 1 2016

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Eph Family Receptors
Hematopoietic Stem Cells
Bone Marrow
Ephrin-B2
Hematopoietic Stem Cell Mobilization
Neoplasms
Neoplastic Stem Cells
Myeloid Cells

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kwak, H., Salvucci, O., Weigert, R., Martinez-Torrecuadrada, J. L., Henkemeyer, M., Poulos, M. G., ... Tosato, G. (2016). Sinusoidal ephrin receptor EPHB4 controls hematopoietic progenitor cell mobilization from bone marrow. Journal of Clinical Investigation, 126(12), 4554-4568. https://doi.org/10.1172/JCI87848

Sinusoidal ephrin receptor EPHB4 controls hematopoietic progenitor cell mobilization from bone marrow. / Kwak, Hyeongil; Salvucci, Ombretta; Weigert, Roberto; Martinez-Torrecuadrada, Jorge L.; Henkemeyer, Mark; Poulos, Michael G.; Butler, Jason M.; Tosato, Giovanna.

In: Journal of Clinical Investigation, Vol. 126, No. 12, 01.12.2016, p. 4554-4568.

Research output: Contribution to journalArticle

Kwak, H, Salvucci, O, Weigert, R, Martinez-Torrecuadrada, JL, Henkemeyer, M, Poulos, MG, Butler, JM & Tosato, G 2016, 'Sinusoidal ephrin receptor EPHB4 controls hematopoietic progenitor cell mobilization from bone marrow', Journal of Clinical Investigation, vol. 126, no. 12, pp. 4554-4568. https://doi.org/10.1172/JCI87848
Kwak, Hyeongil ; Salvucci, Ombretta ; Weigert, Roberto ; Martinez-Torrecuadrada, Jorge L. ; Henkemeyer, Mark ; Poulos, Michael G. ; Butler, Jason M. ; Tosato, Giovanna. / Sinusoidal ephrin receptor EPHB4 controls hematopoietic progenitor cell mobilization from bone marrow. In: Journal of Clinical Investigation. 2016 ; Vol. 126, No. 12. pp. 4554-4568.
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