Ca(2+) Signalling in Endothelial Progenitor Cells: Friend or Foe?

Abstract

Endothelial progenitor cells (EPCs) are mobilized either from the bone marrow and/or the arterial to replace dysfunctional endothelial cells and rescue blood perfusion in ischemic tissues. In addition, they may contribute to the angiogenic switch, thereby sustaining tumour growth and metastatization. Understanding the molecular mechanisms utilized by vascular endothelial growth factor (VEGF) to stimulate EPCs might unveil novel targets to enhance their clinical outcome in regenerative medicine and to adverse tumour vascularisation. VEGF stimulates peripheral blood-derived EPCs to undergo repetitive Ca(2+) oscillations shaped by the interaction between inositol-1,4,5-trisphosphate (InsP3 )-dependent Ca(2+) release and store-operated Ca(2+) entry (SOCE). However, the Ca(2+) machinery underlying VEGF-induced Ca(2+) spikes changes in umbilical cord blood-derived EPCs, which require TRPC3-mediated Ca(2+) entry to trigger the interplay between InsP3 and SOCE. Surprisingly, VEGF fails to elicit pro-angiogenic Ca(2+) signals when EPCs derive from renal cellular carcinoma patients, thus questioning the suitability of VEGFR-2 as a target for anti-angiogenic treatments in these individuals. The lack of response to VEGF is likely due to the dramatic rearrangement of the Ca(2+) toolkit occurring in RCC-derived EPCs. Finally, primary myelofibrosis-derived EPCs display a further pattern of reorganization of the Ca(2+) machinery and proliferate independently of SOCE. Thus, the Ca(2+) machinery in human ECFCs is extremely plastic and may change depending on the physio-pathological background of the donor. As a consequence, the Ca(2+) toolkit could properly be used to enhance the regenerative outcome of cell-based therapy or adverse tumor vascularisation.

• Authors: Francesco Moccia, Germano Guerra
• Journal: Journal of cellular physiology (J Cell Physiol) Vol. 231 Issue 2 Pg. 314-27 (Feb 2016) ISSN: 1097-4652 [Electronic] United States
• PMID: 26247172 (Publication Type: Journal Article, Review)
• Copyright: © 2015 Wiley Periodicals, Inc.

Chemical References

• VEGFA protein, human
• Vascular Endothelial Growth Factor A

Topics

• Animals
• Calcium Signaling
• Carcinoma, Renal Cell (pathology, physiopathology)
• Cell Proliferation
• Cell- and Tissue-Based Therapy
• Endothelial Progenitor Cells (cytology, physiology)
• Fetal Blood (cytology)
• Humans
• Kidney Neoplasms (pathology, physiopathology)
• Models, Biological
• Neovascularization, Pathologic
• Neovascularization, Physiologic
• Primary Myelofibrosis (pathology, physiopathology)
• Vascular Endothelial Growth Factor A (physiology)