title: Knockdown of IGF2R suppresses proliferation and induces apoptosis in hemangioma cells in vitro and in vivo.
abstract: Insulin-like growth factor-II (IGF-II)/IGF2R signaling plays a pivotal role in cell growth, migration and differentiation in many malignancies. An individual with high IGF-II expression levels has a high risk of developing cancer, but IGF2R is often considered to be a tumor suppressor. To date, little has been reported about the role of IGF-II/IGF2R signaling in hemangiomas (HAs). Thus, uncovering the mechanisms of IGF-II/IGF2R signaling is very important to understanding the development of HAs. In the present study, the expression of IGF-II and IGF2R was investigated in 27 cases of HAs of different phases by immunohistochemistry. Through lentivirus-mediated IGF2R siRNA (Lv-siIGF2R) in HA-derived endothelial cells (HDECs), we observed the effects of IGF2R knockdown on the biological behavior of HA cells. We found that the expression of IGF-II and IGF2R was significantly increased in proliferating phase HAs, but decreased in involuting phase HAs. Furthermore, knockdown of IGF2R in vitro significantly diminished the proliferative activity and induced apoptosis and cycle arrest with decreased expression of PCNA, Ki-67, Bcl-2, Cyclin D1 and E and increased the expression of Bax in the proliferative phase HAs (HDEC and CRL-2586 EOMA cells). In addition, the tumor volumes in a subcutaneous HDEC nude mouse model treated with Lv-siIGF2R were significantly smaller than those of the control group. Taken together, our findings indicate that the expression of IGF-II and IGF2R is increased in proliferating phase HAs, and knockdown of IGF2R suppresses proliferation and induces apoptosis in HA cells in vitro and in vivo, suggesting that IGF2R may represent a novel therapeutic target for the treatment of human HAs.
authors: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
authors: J-M
authors: JM
authors: Ou
authors: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
authors: W-S
authors: WS
authors: Lian
authors: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
authors: M-K
authors: MK
authors: Qiu
authors: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
authors: Y-X
authors: YX
authors: Dai
authors: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
authors: Q
authors: Q
authors: Dong
authors: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
authors: J
authors: J
authors: Shen
authors: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
authors: P
authors: P
authors: Dong
authors: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
authors: X-F
authors: XF
authors: Wang
authors: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
authors: Y-B
authors: YB
authors: Liu
authors: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China.
authors: Z-W
authors: ZW
authors: Quan
authors: Department of General Surgery, Xinhua Hospital (Chong Ming) Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 202150, P.R. China.
authors: Z-W
authors: ZW
authors: Fei
mesh_terms: D000818:Animals; D017209:Apoptosis; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques / Q000379:methods*; D015316:Genetic Therapy; D006391:Hemangioma / Q000473:pathology / Q000628:therapy*; D006801:Humans; D066298:In Vitro Techniques; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D017527:Receptor, IGF Type 2 / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D034741:RNA, Small Interfering; D017527:Receptor, IGF Type 2; D007335:Insulin-Like Growth Factor II