scFv-mediated delivery of truncated BID suppresses HER2-positive osteosarcoma growth and metastasis.
Osteosarcoma is the most common primary malignant bone tumor, with high rates of metastasis. Here, we examined the expression of human epidermal growth factor receptor-2 (HER-2) in osteosarcoma cell lines with different metastatic potential, finding that the expression was correlated with metastasis of implanted tumors. We then introduced an expression vector encoding the e23sFv-PEA II-Bid Delta1-60 gene, composed of a HER2-specific single-chain antibody fused with domain II of Pseudomonas exotoxin A (PEA) and the carboxy end of truncated active Bid. We demonstrated that the e23sFv-PEA II-Bid Delta1-60 molecule selectively recognized and killed HER2-overexpressing osteosarcoma cells in vitro. Subsequently, we introduced the e23sFv-PEA II-bid Delta1-60 gene into BALB/c athymic mice bearing HER2-positive osteosarcomas using i.m. injections of liposome-encapsulated vector. Expression of the e23sFv-PEA II-Bid Delta1-60 gene suppressed tumor growth, significantly prolonged animal survival and inhibited metastasis, thereby suggesting it may represent a competitive approach to treating HER2/neu-positive osteosarcoma.
Shan
Le-Qun
LQ
Department of Orthopaedics Surgery, Tangdu Hospital, Xi'an, China.
Qiu
Xiu-Chun
XC
Xu
Yan-Ming
YM
Ji
Zheng-Gang
ZG
Yang
Tong-Tao
TT
Chen
Xiang
X
Ma
Bao-An
BA
Zhou
Yong
Y
Fan
Qing-Yu
QY
Yang
An-Gang
AG
D000818:Animals; D017209:Apoptosis; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D051023:BH3 Interacting Domain Death Agonist Protein / Q000235:genetics* / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods; D006367:HeLa Cells; D006801:Humans; D007128:Immunoglobulin Fragments / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*
D051033:Apoptosis Inducing Factor; D051023:BH3 Interacting Domain Death Agonist Protein; D066246:ErbB Receptors; D007128:Immunoglobulin Fragments; D008081:Liposomes; D018719:Erb-b2 Receptor Tyrosine Kinases