semaphorin-3d and semaphorin-3e inhibit the development of tumors from glioblastoma cells implanted in the cortex of the brainsemaphorin-3d semaphorin-3e抑制肿瘤的发展和胶质母细胞瘤细胞植入大脑皮层.pdfVIP

Semaphorin-3D and Semaphorin-3E Inhibit the Development of Tumors from Glioblastoma Cells Implanted in the Cortex of the Brain 1. 2. 1. 1 2 1 Adi D. Sabag , Julia Bode , Dorit Fink , Boaz Kigel , Wilfried Kugler *, Gera Neufeld * 1 Cancer Research and Vascular Biology Center, The Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel, 2 Department of Pediatric Hematology and Oncology, University of Goettingen, Goettingen, Germany Abstract Class-3 semaphorins are secreted axon guidance factors. Some of these semaphorins have recently been characterized as suppressors of tumor progression. To determine if class-3 semaphorins can be used to inhibit the development of glioblastoma-multiforme tumors, we expressed recombinant sema-3A, 3B, 3D, 3E, 3F or 3G in U87MG glioblastoma cells. Sema3A and sema3B expressing cells contracted and changed shape persistently while cells expressing other semaphorins did not. Sema3A and sema3F differed from other semaphorins including sema3B as they also inhibited the proliferation of the cells and the formation of soft agar colonies. With the exception of sema3G and sema3B, expression of these semaphorins in U87MG cells inhibited significantly tumor development from subcutaneously implanted cells. Strong inhibition of tumor development was also observed following implantation of U87MG cells expressing each of the class-3 semaphorins in the cortex of mouse brains. Sema3D and sema3E displayed the strongest inhibitory effects and their expression in U373MG or in U87MG glioblastoma cells implanted in the brains of mice prolonged the survival of the mic