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Ca 2+ Signalling in Endothelial Progenitor Cells: Friend or Foe?
Author(s) -
Moccia Francesco,
Guerra Germano
Publication year - 2016
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.25126
Subject(s) - trpc3 , progenitor cell , vascular endothelial growth factor , angiogenesis , microbiology and biotechnology , orai1 , bone marrow , cancer research , medicine , trpc , stem cell , chemistry , biology , stim1 , vegf receptors , calcium , receptor , transient receptor potential channel
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 (InsP 3 )‐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 InsP 3 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. J. Cell. Physiol. 231: 314–327, 2016. © 2015 Wiley Periodicals, Inc.