miR-126-3p is essential for CXCL12-induced angiogenesis.

Atherosclerosis, in the ultimate stage of cardiovascular diseases, causes an obstruction of vessels leading to ischemia and finally to necrosis. To restore vascularization and tissue regeneration, stimulation of angiogenesis is necessary. Chemokines and microRNAs (miR) were studied as pro-angiogenic agents.

Identification of a Pro-Angiogenic Potential and Cellular Uptake Mechanism of a LMW Highly Sulfated Fraction of Fucoidan from Ascophyllum nodosum.

Herein we investigate the structure/function relationships of fucoidans from to analyze their pro-angiogenic effect and cellular uptake in native and glycosaminoglycan-free (GAG-free) human endothelial cells (HUVECs). Fucoidans are marine sulfated polysaccharides, which act as glycosaminoglycans mimetics. We hypothesized that the size and sulfation rate of fucoidans influence their ability to induce pro-angiogenic processes independently of GAGs.

Heparanase and Syndecan-4 Are Involved in Low Molecular Weight Fucoidan-Induced Angiogenesis.

Induction of angiogenesis is a potential treatment for chronic ischemia. Low molecular weight fucoidan (LMWF), the sulfated polysaccharide from brown seaweeds, has been shown to promote revascularization in a rat limb ischemia, increasing angiogenesis in vivo. We investigated the potential role of two heparan sulfate (HS) metabolism enzymes, exostosin-2 (EXT2) and heparanase (HPSE), and of two HS-membrane proteoglycans, syndecan-1 and -4 (SDC-1 and SDC-4), in LMWF induced angiogenesis.

RANTES/CCL5 mediated-biological effects depend on the syndecan-4/PKCα signaling pathway.

The perpetuation of angiogenesis is involved in certain chronic inflammatory diseases. The accelerated neovascularisation may result from an inflammatory status with a response of both endothelial cells and monocytes to inflammatory mediators such as chemokines. We have previously described in vitro and in vivo the pro-angiogenic effects of the chemokine Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES)/CCL5.

Synthesis and biological evaluation of new bisphosphonate-dextran conjugates targeting breast primary tumor.

Bisphosphonates (BPs) have interesting antitumor effects as well in vitro as in vivo, despite their poor bioavailability in the organism after oral ingestion. To overcome this problem and reduce drug doses and secondary effects, we report the chemical synthesis of new bioconjugates. They were built with a nitrogen-containing BP as the drug covalently coupled to the carboxymethyldextran.

Angiogenic properties of the chemokine RANTES/CCL5.

Atherosclerosis is an inflammatory disease that is one of the leading causes of death in developed countries. This disease is defined by the formation of an atherosclerotic plaque, which is responsible for artery obstruction and affects the heart by causing myocardial infarction. The vascular wall is composed of three cell types and includes a monolayer of endothelial cells and is irrigated by a vasa vasorum.

Low molecular weight fucoidan prevents intimal hyperplasia in rat injured thoracic aorta through the modulation of matrix metalloproteinase-2 expression.

The therapeutic potential of low molecular-weight fucoidan (LMWF), a sulfated polysaccharide extracted from brown seaweed was investigated on vascular smooth muscle cell (VSMC) and human vascular endothelial cell (HUV-EC-C) proliferation and migration in vitro and in a rat model of intimal hyperplasia. Sprague-Dawley rats were subjected to balloon injury in the thoracic aorta followed by two weeks' treatment with either LMWF (5mg/kg/day) or vehicle. Morphological analysis and proliferating cell nuclear antigen immunostaining at day 14 indicated that LMWF prevented intimal hyperplasia in rat thoracic aorta as compared with vehicle (neo-intima area, 3±0.

Glycosaminoglycan mimetics inhibit SDF-1/CXCL12-mediated migration and invasion of human hepatoma cells.

We have recently reported that the CXC-chemokine stromal cell-derived factor-1 (SDF-1)/CXCL12 induces proliferation, migration, and invasion of the Huh7 human hepatoma cells through its G-protein-coupled receptor CXCR4 and that glycosaminoglycans (GAGs) are involved in these events. Here, we demonstrate by surface plasmon resonance that the chemokine binds to GAG mimetics obtained by grafting carboxylate, sulfate or acetate groups onto a dextran backbone. We also demonstrate that chemically modified dextrans inhibit SDF-1/CXCL12-mediated in vitro chemotaxis and anchorage-independent cell growth in a dose-dependent manner.

Monocyte chemoattractant protein-1 (MCP-1)/CCL2 secreted by hepatic myofibroblasts promotes migration and invasion of human hepatoma cells.

The aim of our study was to investigate whether myofibroblasts and the chemokine monocyte chemoattractant protein-1 (MCP-1)/CCL2 may play a role in hepatocellular carcinoma progression. We observed that hepatic myofibroblast LI90 cells express MCP-1/CCL2 mRNA and secrete this chemokine. Moreover, myofibroblast LI90 cell-conditioned medium (LI90-CM) induces human hepatoma Huh7 cell migration and invasion.

Syndecan-1 and syndecan-4 are involved in RANTES/CCL5-induced migration and invasion of human hepatoma cells.

Background: We previously demonstrated that the CC-chemokine Regulated upon Activation, Normal T cell Expressed and Secreted (RANTES)/CCL5 exerts pro-tumoral effects on human hepatoma Huh7 cells through its G protein-coupled receptor, CCR1. Glycosaminoglycans play major roles in these biological events.

Methods: In the present study, we explored 1/ the signalling pathways underlying RANTES/CCL5-mediated hepatoma cell migration or invasion by the use of specific pharmacological inhibitors, 2/ the role of RANTES/CCL5 oligomerization in these effects by using a dimeric RANTES/CCL5, 3/ the possible involvement of two membrane heparan sulfate proteoglycans, syndecan-1 (SDC-1) and syndecan-4 (SDC-4) in RANTES/CCL5-induced cell chemotaxis and spreading by pre-incubating cells with specific antibodies or by reducing SDC-1 or -4 expression by RNA interference.

A prenylation inhibitor (sodium phenylacetate) differently affects MCF-7 cell death when ras is overexpressed, partly involving P42/44, JNK and P38 kinase activations.

Background: Sodium phenylacetate (NaPa) inhibits breast cancer cell proliferation decreasing prenylation of small G proteins including Ras.

Materials And Methods: Aponecrosis induced by NaPa in MCF-7 and MCF-7ras breast cancer cells was evaluated by measuring Annexin V/PI labelling by flow cytometry. Specific inhibitors of p42/44 (PD 98059), p38 (SB 600125) and JNK (SP 202190) in association with NaPa were also tested.

A new dimethyl ester bisphosphonate inhibits angiogenesis and growth of human epidermoid carcinoma xenograft in nude mice.

Bisphosphonates are extensively used in the treatment of patients with metastasis-induced osteolysis. The major drawback in the efficacy of all bisphosphonates lies in their high hydrophilic nature, which results in poor membrane permeability and low availability for soft tissues. A reasonable approach to overcome these problems consists in masking one or more ionizable groups of bisphosphonates, notably by esterification of the hydroxyl functions.

Alendronate inhibits proliferation and invasion of human epidermoid carcinoma cells in vitro.

There is increasing evidence that bisphosphonates have direct antitumor effects in vivo in addition to their therapeutic antiresorptive properties. Bisphosphonates inhibit proliferation and induce apoptosis of many cancer cell lines. They also exhibit anti-invasive properties in vitro and in vivo.

Structure-activity relationships of a new class of aromatic bisphosphonates that inhibit tumor cell proliferation in vitro.

We previously reported a simple and efficient one-pot procedure for synthesis of 1-hydroxymethylene-1,1-bisphosphonic acids (HMBP). According to this method, we synthesized a series of new aromatic HMBP and investigated structure-activity relationships by evaluating their anti-proliferative activity against A431 human tumor cell line. Our results showed that the introduction of an extra methylene group in a pyridyl-containing R2 side chain increased 100-fold the anti-proliferative activity of the HMBP.

A novel non-containing-nitrogen bisphosphonate inhibits both in vitro and in vivo angiogenesis.

Bisphosphonates (BP) are powerful inhibitors of bone resorption and are widely used in the treatment of patients with metastasis-induced osteolysis. In the present study, we show that a novel non-nitrogen-containing BP (BP7033) that exhibits antitumor activity is a potent inhibitor of both in vivo and in vitro angiogenesis. When administered to mice, BP7033 inhibited tumoral angiogenesis (65% at 0.