PAI-1 mediates antiangiogenic and fibrinolytic actions of prolactin/growth hormone 16-14K fragments

Poster (2011, January)

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

in Endocrinology (2011)

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 ... [more ▼]

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. [less ▲]

Prevention of bacterial biofilms onto stainless steel substrates by immobilization of antimicrobial and anti-biofilm biomolecules

Conference (2011)

Stainless steel is widely used in the daily life in building and food industries as well as in the medical field. However, at long term, bacteria succeed in adhering, proliferating and forming a resistant ... [more ▼]

Stainless steel is widely used in the daily life in building and food industries as well as in the medical field. However, at long term, bacteria succeed in adhering, proliferating and forming a resistant biofilm on stainless steel. Therefore, surface modification is needed providing metal surface with antibacterial, anti-adhesion and easy cleaning properties. Several biomolecules (antimicrobial peptides, antiadhesion biomolecules and anti-biofilm enzymes) were immobilized on stainless steel thanks to different immobilization techniques. In a first approach, cationic peptides have been embedded in a LBL architecture comprising anti-adhesion biomolecules. In a second approach, small inorganic-binding peptides isolated by phage display technology and recognizing specifically the steel surface were used as linker for antimicrobial peptide immobilization. Finally, antibacterial peptides were covalently grafted onto an organic-polymeric interlayer deposited by plasma. Resulting antibacterial, antiadhesion and anti-biofilm properties were characterized and the advantages of each immobilization technique were documented. The biocidal effect of these surfaces was demonstrated against Gram+/- bacteria. Coated stainless steel surfaces led to 95% reduction of S. epidermidis adhesion vs bare substrate. By combining both antibacterial and anti-adhesion biomolecules, we produced stainless steel surfaces with better cleanability. A biofilm-releasing glycoside hydrolase was also immobilized on the surface and showed to confer anti-biofilm properties to stainless steel. Moreover, we provide valuable insight about the resistance of the coating to close to real life cleaning conditions. [less ▲]

MicroRNA-21 Exhibits Antiangiogenic Function by Targeting RhoB Expression in Endothelial Cells.

in PLoS ONE (2011), 6(2), 16979

BACKGROUND: MicroRNAs (miRNAs) are endogenously expressed small non-coding RNAs that regulate gene expression at post-transcriptional level. The recent discovery of the involvement of these RNAs in the ... [more ▼]

BACKGROUND: MicroRNAs (miRNAs) are endogenously expressed small non-coding RNAs that regulate gene expression at post-transcriptional level. The recent discovery of the involvement of these RNAs in the control of angiogenesis renders them very attractive in the development of new approaches for restoring the angiogenic balance. Whereas miRNA-21 has been demonstrated to be highly expressed in endothelial cells, the potential function of this miRNA in angiogenesis has never been investigated. METHODOLOGY/PRINCIPAL FINDINGS: We first observed in endothelial cells a negative regulation of miR-21 expression by serum and bFGF, two pro-angiogenic factors. Then using in vitro angiogenic assays, we observed that miR-21 acts as a negative modulator of angiogenesis. miR-21 overexpression reduced endothelial cell proliferation, migration and the ability of these cells to form tubes whereas miR-21 inhibition using a LNA-anti-miR led to opposite effects. Expression of miR-21 in endothelial cells also led to a reduction in the organization of actin into stress fibers, which may explain the decrease in cell migration. Further mechanistic studies showed that miR-21 targets RhoB, as revealed by a decrease in RhoB expression and activity in miR-21 overexpressing cells. RhoB silencing impairs endothelial cell migration and tubulogenesis, thus providing a possible mechanism for miR-21 to inhibit angiogenesis. Finally, the therapeutic potential of miR-21 as an angiogenesis inhibitor was demonstrated in vivo in a mouse model of choroidal neovascularization. CONCLUSIONS/SIGNIFICANCE: Our results identify miR-21 as a new angiogenesis inhibitor and suggest that inhibition of cell migration and tubulogenesis is mediated through repression of RhoB. [less ▲]

Biomimetic coatings with robust antibacterial properties

Conference (2010, July 01)

Nanocoatings of inorganic surfaces by molecular biomimetic

Poster (2010, June 30)

miR-146a: an anti-angiogenic miRNA regulated by NF-kB

Poster (2010, May 21)

16K human prolactin is an anti-lymphangiogenic factor in vitro and in vivo

Poster (2010, May 21)

Study of the role of miR-21 in the regulation of angiogenesis

Poster (2010, May)

A robust antibacterial coating for stainless steel

Conference (2010, March 23)

Because of corrosion, chemical resistance, relevant mechanical and esthetical properties, stainless steel is widely used in the daily life, not only in the building industry but also in the food industry ... [more ▼]

Because of corrosion, chemical resistance, relevant mechanical and esthetical properties, stainless steel is widely used in the daily life, not only in the building industry but also in the food industry, the appliances or in the medical field, including implants in orthopedic surgery. However, stainless steel is unable to prevent bacteria from adhering, proliferating and forming a resistant biofilm. Therefore, surface modification is needed for providing the metal surface with antibacterial properties. The scientific literature is very rich in describing various methods for imparting antibacterial properties to different inorganic supports. However, the activity of the coating is generally time limited by the diffusion of the biocide in the environment. Novel robust and stable antibacterial coatings on stainless steel are thus highly desirable for the durability of the functionality. In this communication, we report on an all-in-one approach to prepare robust antimicrobial films on stainless steel using the layer-by-layer deposition of polyelectrolytes. Novel biocidal multilayered polyelectrolyte films in which the polycationic layer is silver loaded and bears 3,4-dihydroxyphenylalanine (DOPA), known as a promoter of adhesion to inorganic surfaces, were deposited onto stainless steel. DOPA was incorporated in the polycationic chains by radical copolymerisation of N-methacrylated DOPA with the commercially available quaternary ammonium salt of 2-(dimethylamino)ethyl methacrylate (DMAEMA+). Polystyrene sulfonate (PSS) was the polyanionic constituent of the films. In order to boost the antibacterial activity of the polycationic layer, AgNO3 was added to the aqueous solution of P(DOPA)-co-P(DMAEMA+), which resulted in the in-situ formation of silver based nanoparticles (Ag° and AgCl) that are sources of biocial Ag+. The layer-by-layer deposition of aqueous P(DOPA)-co-P(DMAEMA+)/AgCl/Ag0 suspension and aqueous solution of PSS provides stainless steel with high antibacterial activity against Gram-negative E. Coli bacteria. Moreover, after silver depletion, films retain some antimicrobial activity, thanks to the ammonium groups of the copolymer. We will also show how the antibacterial activity of the films can then be easily re-boosted. The multi-functionality of the P(DOPA)-co-P(DMAEMA+) is a key issue in this process (i) the DOPA co-units are anchored to stainless steel, (ii) these co-units reduce partly AgNO3 into Ag0 nanoparticles and stabilize them by chelation, (iii) the chloride counter-anions react with AgNO3 by ionic exchange, leading to the in situ formation of AgCl particles, and (iv) the ammonium groups are responsible for permanent antibacterial activity. Besides the advantage of the all-in-one process, another major advantage of the approach proposed here is the implementation of the whole process of film formation, including the synthesis of P(DOPA)-co-P(DMAEMA+), in aqueous media under very mild conditions. It makes the strategy very attractive for industrial scaling-up and sustainability applications. [less ▲]