Growth of human squamous cell carcinoma xenografts in mice is inhibited by local angiostatin gene therapy.
The possibility of inhibiting tumor growth by blocking the formation of new tumor vessels has recently received attention. Antiangiogenic tumor therapies have recently attracted intense interest because of their direct endothelial targeting and the absence of drug resistance. Local antiangiogenic gene therapy for cancer offers a potential way to achieve sustained therapeutic release of antiangiogenic substances. As a step toward this goal, we used liposomes complexed to angiostatin cDNA and targeted to human squamous cell carcinoma cell lines in vivo. Tumor cells expressing angiostatin after local gene transfer showed markedly reduced vascularity and contained many apoptotic tumor cells. These results demonstrate the potential utility of liposome-derived angiostatin for adjuvant therapy of oral cancer in humans.
Matsumoto
G
G
First Department of Oral and Maxillofacial Surgery, Kanagawa Dental College, 82 Inaoka, Yokosuka, Kanagawa, Japan. gmatsu@kdcnet.ac.jp
Sasakuri
K
K
Tsukinoki
K
K
Ohmi
Y
Y
Lee
U
U
Shindo
J
J
D043168:Angiostatins; D000818:Animals; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000098:blood supply* / Q000473:pathology / Q000628:therapy*; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D018390:Gene Targeting / Q000379:methods; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D010958:Plasminogen / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D008081:Liposomes; D010446:Peptide Fragments; D043168:Angiostatins; D010958:Plasminogen