Calcium Signaling pp 1013-1030 | Cite as

Calcium Signaling in Endothelial Colony Forming Cells in Health and Disease

  • Francesco MocciaEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1131)


Endothelial colony forming cells (ECFCs) represent the only known truly endothelial precursors. ECFCs are released in peripheral circulation to restore the vascular networks dismantled by an ischemic insult or to sustain the early phases of the angiogenic switch in solid tumors. A growing number of studies demonstrated that intracellular Ca2+ signaling plays a crucial role in driving ECFC proliferation, migration, homing and neovessel formation. For instance, vascular endothelial growth factor (VEGF) triggers intracellular Ca2+ oscillations and stimulates angiogenesis in healthy ECFCs, whereas stromal derived factor-1α promotes ECFC migration through a biphasic Ca2+ signal. The Ca2+ toolkit endowed to circulating ECFCs is extremely plastic and shows striking differences depending on the physiological background of the donor. For instance, inositol-1,4,5-trisphosphate-induced Ca2+ release from the endoplasmic reticulum is downregulated in tumor-derived ECFCs, while agonists-induced store-operated Ca2+ entry is up-regulated in renal cellular carcinoma and is unaltered in breast cancer and reduced in infantile hemangioma. This remodeling of the Ca2+ toolkit prevents VEGF-induced pro-angiogenic Ca2+ oscillations in tumor-derived ECFCs. An emerging theme of research is the dysregulation of the Ca2+ toolkit in primary myelofibrosis-derived ECFCs, as this myeloproliferative disorder may depend on a driver mutation in the calreticulin gene. In this chapter, I provide a comprehensive, but succinct, description on the architecture and role of the intracellular Ca2+ signaling toolkit in ECFCs derived from umbilical cord blood and from peripheral blood of healthy donors, cancer patients and subjects affected by primary myelofibrosis.


Endothelial colony forming cells Ca2+ signaling Inositol-1,4,5-trisphosphate receptors Two-pore channel 1 STIM1 Orai1 TRPC1 TRPC3 VEGF SDF-1α 


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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Laboratory of General Physiology, Department of Biology and Biotechnology “L. Spallanzani”University of PaviaPaviaItaly

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