Growth of human melanoma xenografts is suppressed by systemic angiostatin gene therapy

Abstract

The effect of local and systemic delivery of the angiostatin gene on human melanoma growth was studied in nude mice. Liposomecoated plasmids carrying the cDNA coding for murine and human angiostatin ( CMVang and BSHang ) were injected weekly, locally or systemically, in mice transplanted with melanoma cells. The treatment reduced melanoma growth by 50% to 90% compared to that occurring in control animals treated with liposome -coated plasmid carrying the lacZ gene or in untreated controls. The growth of both locally injected and controlateral uninjected tumors in mice bearing two melanoma grafts was significantly suppressed after intratumoral treatment. Tumor growth inhibition was also observed in mice treated by intraperitoneal delivery, suggesting that angiostatin gene therapy acts through a systemic effect. Both melanoma growth suppression and delay in the onset of tumor growth were observed in treated mice. PCR performed on tumors and normal tissues showed that the lipofected DNA was present in tissues from treated mice, and angiostatin expression was demonstrated by RT -PCR. Histopathological analysis of melanoma nodules revealed an increase in apoptotic cells and a reduction in vessel density in tumors from treated mice. Our results suggest that systemic, liposome -mediated administration of genes coding for antiangiogenic factors represents a promising strategy for melanoma treatment in humans. Cancer Gene Therapy ( 2001 ) 8, 491 ± 496

A Fragment of Histidine-Rich Glycoprotein Is a Potent Inhibitor of Tumor Vascularization

“…Total cell lysate was separated and blotted for FGFR-1, Erk 1/2 protein, or phospho-Erk 1/2. (37,38). In addition, the proportion of proliferating tumor cells was significantly decreased in HRGP-treated animals.…”

Overexpression of Pigment Epithelium-Derived Factor Decreases Angiogenesis and Inhibits the Growth of Human Malignant Melanoma Cells in Vivo

“…Previous studies have shown that malignant melanoma responds well to antiangiogenic therapy using other endogenous angiogenic inhibitors such as angiostatin (plasminogen kringles 1 to 4) and endostatin. 18,19 Because plasminogen kringle 5 was recently reported to inhibit ischemia-induced retinal neovascularization in a rat model by down-regulating VEGF and up-regulating PEDF, 20 the anti-angiogenic and growth inhibitory effects of angiostatin on melanoma cells could be ascribed, at least in part, to this PEDF activity.…”

Antiangiogenic gene therapy of cancer: recent developments

“…The cationic liposomes can significantly improve systemic delivery and gene expression of DNA [110]. Systemic, liposome-mediated administration of angiostatin could suppress the growth of melanoma tumors in mice [111]. Similar findings were observed by Chen and co-workers with angiostatin and endostatin [112].…”