title: Propranolol enhanced adipogenesis instead of induction of apoptosis of hemangiomas stem cells.
abstract: Propranolol has been widely used in treating infantile hemangiomas (IHs). But recurrence of IHs was found in some cases on cessation of propranolol treatment. The other is that Chinese individuals reacted to propranolol differently from American Whites. Whether the difference of sensitivity is due to the β adrenoceptor (β-AR) expression pattern of hemangioma initiating cells remains unclear. In the present study, we isolated hemangioma-derived stem cells (hemSCs) from proliferative IHs and analyzed the biological characteristics and β-AR expression pattern of hemSCs by immunostaining, Western blotting and multilineage differentiation assay as well. We also tested the effects of propranolol on hemSCs by evaluating VEGF expression, proliferation and apoptosis related parameters. Our results indicated that CD133(+) hemSCs located pre-vascular in proiferative IH tissues. Both β1 and β2-AR were expressed, while β2-AR was dominant on hemSCs. Propranolol at 100-150 μM inhibited proliferation of hemSCs, not did 50 μM. Propranolol down-regulated VEGF expression of hemSCs, instead of inducing apoptosis. The adipogenic potential was enhanced by propranolol. Therefore, our current results suggested propranolol could not induce apoptosis of hemSCs, but played a curative role though suppressing VEGF synthesis and enhancement of adipogenesis of hemSCs. Our results might partially provide the insight of mechanism of relapse in some cases on cessation of propranolol treatment.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China.
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Plastic and Reconstructive Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China.
authors.forename: Tinghui
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Department of Plastic and Reconstructive Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China.
authors.forename: Tianxiang
authors.initials: T
authors.lastname: Ouyang
authors.affiliation: Department of Nursing, Huadong Hospital, Shanghai Fudan University Shanghai, China.
authors.forename: Shujia
authors.initials: S
authors.lastname: Xin
authors.affiliation: Department of Plastic and Reconstructive Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China.
authors.forename: Yueting
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Plastic and Reconstructive Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China.
authors.forename: Mengling
authors.initials: M
authors.lastname: Chang
mesh_terms: D050156:Adipogenesis / Q000187:drug effects*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D019008:Drug Resistance, Neoplasm; D005260:Female; D006391:Hemangioma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D011433:Propranolol / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000970:Antineoplastic Agents; D011943:Receptors, Adrenergic, beta; D011433:Propranolol
keywords: Propranolol; hemangioma-stem cells; relapse; β adrenoceptor