title: α6-Integrin is required for the adhesion and vasculogenic potential of hemangioma stem cells.
abstract: 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. α6-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 α6-integrin in HemSC. We documented α6-integrin expression in IH tumor specimens and HemSC by RT-qPCR and flow cytometry. We examined the effect of blocking or silencing α6-integrin on the adhesive and proliferative properties of HemSC in vitro and the vasculogenic and homing properties of HemSC in vivo. Targeting α6-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 α6-integrin siRNA-transfected HemSC. In conclusion, α6-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 α6 integrin in the vasculogenic properties of HemSC. Our results suggest that α6-integrin expression on HemSC could be a new target for antihemangioma therapy.
authors.affiliation: Vascular Biology Program and Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA; Paris Descartes University, Sorbonne Paris Cite, Paris, France; AP-HP, Hôpital Européen Georges Pompidou, Department of Hematology, Paris, France.
authors.forename: David M
authors.initials: DM
authors.lastname: Smadja
authors.forename: Coralie L
authors.initials: CL
authors.lastname: Guerin
authors.forename: Elisa
authors.initials: E
authors.lastname: Boscolo
authors.forename: Ivan
authors.initials: I
authors.lastname: Bieche
authors.forename: John B
authors.initials: JB
authors.lastname: Mulliken
authors.forename: Joyce
authors.initials: J
authors.lastname: Bischoff
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation; D002675:Child, Preschool; D005260:Female; D055785:Gene Knockdown Techniques; D006391:Hemangioma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007223:Infant; D039503:Integrin alpha6 / Q000378:metabolism*; D007797:Laminin / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology*
chemical_list: D039503:Integrin alpha6; D007797:Laminin
keywords: Adhesion; Fluorescence molecular tomography; Hemangioma stem cells; Vasculogenesis; α6-Integrin
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