Antiangiogenic liposomal gene therapy with 16K human prolactin efficiently reduces tumor growth

Kinet, Virginie; Nguyen, Ngoc-Quynh-Nhu; Sabatel, Céline; Blacher, Silvia; Noël, Agnès; Martial, Joseph; Struman, Ingrid

doi:10.1016/j.canlet.2009.04.030

Cited by 23 publications

(14 citation statements)

References 24 publications

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“…16 K hPRL is able to inhibit tumor growth and metastasis in various mouse models by inhibiting neovascularization [12-15]. The potential therapeutic use of 16 K hPRL has also been observed in non-cancer pathological models like retinopathy [16].…”

Section: Introductionmentioning

confidence: 99%

Sprouty1, a new target of the angiostatic agent 16K prolactin, negatively regulates angiogenesis

et al. 2010

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BackgroundDisorganized angiogenesis is associated with several pathologies, including cancer. The identification of new genes that control tumor neovascularization can provide novel insights for future anti-cancer therapies. Sprouty1 (SPRY1), an inhibitor of the MAPK pathway, might be one of these new genes. We identified SPRY1 by comparing the transcriptomes of untreated endothelial cells with those of endothelial cells treated by the angiostatic agent 16 K prolactin (16 K hPRL). In the present study, we aimed to explore the potential function of SPRY1 in angiogenesis.ResultsWe confirmed 16 K hPRL induced up-regulation of SPRY1 in primary endothelial cells. In addition, we demonstrated the positive SPRY1 regulation in a chimeric mouse model of human colon carcinoma in which 16 K hPRL treatment was shown to delay tumor growth. Expression profiling by qRT-PCR with species-specific primers revealed that induction of SPRY1 expression by 16 K hPRL occurs only in the (murine) endothelial compartment and not in the (human) tumor compartment. The regulation of SPRY1 expression was NF-κB dependent. Partial SPRY1 knockdown by RNA interference protected endothelial cells from apoptosis as well as increased endothelial cell proliferation, migration, capillary network formation, and adhesion to extracellular matrix proteins. SPRY1 knockdown was also shown to affect the expression of cyclinD1 and p21 both involved in cell-cycle regulation. These findings are discussed in relation to the role of SPRY1 as an inhibitor of ERK/MAPK signaling and to a possible explanation of its effect on cell proliferation.ConclusionsTaken together, these results suggest that SPRY1 is an endogenous angiogenesis inhibitor.

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Section: Introductionmentioning

confidence: 99%

Sprouty1, a new target of the angiostatic agent 16K prolactin, negatively regulates angiogenesis

et al. 2010

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“…These results are in line with our previous publications in which we used B16F10 tumor cells in a sc flank model. 16K hPRL treatment reduced blood vessel area and decreased the vessel number, which combined lead to globally reduced vessel density (18,19).…”

Section: K Hprl Delays Tumor Growth and Impedes Neovascularization mentioning

confidence: 99%

“…Image processing and measurements were performed with the Aphelion 3.2 software from Adsis (Hérou-ville, France) on a personal computer as described previously (18,19). Briefly, complete tumor and lymph node sections were analyzed for each condition.…”

Section: Image Processing and Measurementsmentioning

confidence: 99%

“…Furthermore, Kim et al (17) demonstrated that adenovirus-mediated 16K hPRL expression by prostate cancer cells decreases tumor growth. Studies in our laboratory on the B16F10 mouse melanoma tumor model showed a significant tumor growth delay after 16K hPRL treatment and distinct tumor vasculature characterized by small and narrow vessels (18,19). Additionally, Nguyen et al (19) demonstrated in an experimental lung metastasis model via iv injection of B16F10 melanoma cells without the development of a primary tumor that 16K hPRL treatment of mice before intravenous tumor inoculation decreased tumor metastasis in the lungs.…”

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confidence: 95%

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The Angiostatic Protein 16K Human Prolactin Significantly Prevents Tumor-Induced Lymphangiogenesis by Affecting Lymphatic Endothelial Cells

et al. 2011

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The 16-kDa angiostatic N-terminal fragment of human prolactin (16K hPRL) has been reported to be a new potent anticancer compound. This protein has already proven its efficiency in several mouse tumor models in which it prevented tumor-induced angiogenesis and delayed tumor growth. In addition to angiogenesis, tumors also stimulate the formation of lymphatic vessels, which contribute to tumor cell dissemination and metastasis. However, the role of 16K hPRL in tumor-induced lymphangiogenesis has never been investigated. We establish in vitro that 16K hPRL induces apoptosis and inhibits proliferation, migration, and tube formation of human dermal lymphatic microvascular endothelial cells. In addition, in a B16F10 melanoma mouse model, we found a decreased number of lymphatic vessels in the primary tumor and in the sentinel lymph nodes after 16K hPRL treatment. This decrease is accompanied by a significant diminished expression of lymphangiogenic markers in primary tumors and sentinel lymph nodes as determined by quantitative RT-PCR. These results suggest, for the first time, that 16K hPRL is a lymphangiostatic as well as an angiostatic agent with antitumor properties.

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“…Major nonviral vectors used in gene therapy include circular plasmid or linear DNA complexed with nanoparticles [187, 188] or liposomes (cationic lipid-DNA complex) [189, 190]. Plasmid DNA can be transferred into the cells using a gene gun [191] where the DNA is bound to high density particles like gold and transferred at high velocities into the cell [192] or by electroporation [193], using transposable elements [194] or DNA:RNA oligonucleotide hybrids [195].…”

Section: Gene Therapy Vectorsmentioning

confidence: 99%

Scavenger Receptors and Their Potential as Therapeutic Targets in the Treatment of Cardiovascular Disease

Stephen

Freestone

Dunn

et al. 2010

International Journal of Hypertension

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Scavenger receptors act as membrane-bound and soluble proteins that bind to macromolecular complexes and pathogens. This diverse supergroup of proteins mediates binding to modified lipoprotein particles which regulate the initiation and progression of atherosclerotic plaques. In vascular tissues, scavenger receptors are implicated in regulating intracellular signaling, lipid accumulation, foam cell development, and cellular apoptosis or necrosis linked to the pathophysiology of atherosclerosis. One approach is using gene therapy to modulate scavenger receptor function in atherosclerosis. Ectopic expression of membrane-bound scavenger receptors using viral vectors can modify lipid profiles and reduce the incidence of atherosclerosis. Alternatively, expression of soluble scavenger receptors can also block plaque initiation and progression. Inhibition of scavenger receptor expression using a combined gene therapy and RNA interference strategy also holds promise for long-term therapy. Here we review our current understanding of the gene delivery by viral vectors to cells and tissues in gene therapy strategies and its application to the modulation of scavenger receptor function in atherosclerosis.

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Antiangiogenic liposomal gene therapy with 16K human prolactin efficiently reduces tumor growth

Cited by 23 publications

References 24 publications

Sprouty1, a new target of the angiostatic agent 16K prolactin, negatively regulates angiogenesis

Sprouty1, a new target of the angiostatic agent 16K prolactin, negatively regulates angiogenesis

The Angiostatic Protein 16K Human Prolactin Significantly Prevents Tumor-Induced Lymphangiogenesis by Affecting Lymphatic Endothelial Cells

Scavenger Receptors and Their Potential as Therapeutic Targets in the Treatment of Cardiovascular Disease

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