title: Multiple delivery of siRNA against endoglin into murine mammary adenocarcinoma prevents angiogenesis and delays tumor growth.
abstract: Endoglin is a transforming growth factor-β (TGF- β) co-receptor that participates in the activation of a signaling pathway that mediates endothelial cell proliferation and migration in angiogenic tumor vasculature. Therefore, silencing of endoglin expression is an attractive approach for antiangiogenic therapy of tumors. The aim of our study was to evaluate the therapeutic potential of small interfering RNA (siRNA) molecules against endoglin in vitro and in vivo. Therapeutic potential in vitro was assessed in human and murine endothelial cells (HMEC-1, 2H11) by determining endoglin expression level, cell proliferation and tube formation. In vivo, the therapeutic potential of siRNA molecules was evaluated in TS/A mammary adenocarcinoma growing in BALB/c mice. Results of our study showed that siRNA molecules against endoglin have a good antiangiogenic therapeutic potential in vitro, as expression of endoglin mRNA and protein levels in mouse and human microvascular endothelial cells after lipofection were efficiently reduced, which resulted in the inhibition of endothelial cell proliferation and tube formation. In vivo, silencing of endoglin with triple electrotransfer of siRNA molecules into TS/A mammary adenocarcinoma also significantly reduced the mRNA levels, number of tumor blood vessels and the growth of tumors. The obtained results demonstrate that silencing of endoglin is a promising antiangiogenic therapy of tumors that could not be used as single treatment, but as an adjunct to the established cytotoxic treatment approaches.
authors.affiliation: Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors.forename: Tanja
authors.initials: T
authors.lastname: Dolinsek
authors.forename: Bostjan
authors.initials: B
authors.lastname: Markelc
authors.forename: Gregor
authors.initials: G
authors.lastname: Sersa
authors.forename: Andrej
authors.initials: A
authors.lastname: Coer
authors.forename: Monika
authors.initials: M
authors.lastname: Stimac
authors.forename: Jaka
authors.initials: J
authors.lastname: Lavrencak
authors.forename: Andreja
authors.initials: A
authors.lastname: Brozic
authors.forename: Simona
authors.initials: S
authors.lastname: Kranjc
authors.forename: Maja
authors.initials: M
authors.lastname: Cemazar
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000473:pathology / Q000628:therapy*; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018274:Electroporation; D000071063:Endoglin; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000517:prevention & control; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D014162:Transfection; D047368:Tumor Burden
chemical_list: D000071063:Endoglin; C502004:Eng protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering