α6-Integrin Is Required for the Adhesion and Vasculogenic Potential of Hemangioma Stem Cells

Infantile hemangioma (IH) is the most common tumor of infancy. Hemangioma stem cells (HemSC) are a mesenchymal subpopulation isolated from IH CD133+ cells. HemSC can differentiate into endothelial and pericyte/smooth muscle cells and form vascular networks when injected in immune-deficient mice. alpha 6-Integrin subunit has been implicated in the tumorgenicity of glioblastoma stem cells and the homing properties of hematopoietic, endothelial, and mesenchymal progenitor cells. Therefore, we investigated the possible function(s) of alpha 6-integrin in HemSC. We documented alpha 6-integrin expression in IH tumor specimens and HemSC by RT-qPCR and flow cytometry. We examined the effect of blocking or silencing alpha 6-integrin on the adhesive and proliferative properties of HemSC in vitro and the vasculogenic and homing properties of HemSC in vivo. Targeting alpha 6-integrin in cultured HemSC inhibited adhesion to laminin but had no effect on proliferation. Vessel-forming ability in Matrigel implants and hepatic homing after i.v. delivery were significantly decreased in alpha 6-integrin siRNA-transfected HemSC. In conclusion, alpha 6-integrin is required for HemSC adherence to laminin, vessel formation in vivo, and for homing to the liver. Thus, we uncovered an important role for alpha 6 integrin in the vasculogenic properties of HemSC. Our results suggest that alpha 6-integrin expression on HemSC could be a new target for antihemangioma therapy. Stem Cells 2014;32:684-693