Syndecan-1 Enhances Proliferation, Migration and Metastasis of HT-1080 Cells in Cooperation with Syndecan-2

Syndecans are transmembrane heparan sulphate proteoglycans. Their role in the development of the malignant phenotype is ambiguous and depends upon the particular type of cancer. Nevertheless, syndecans are promising targets in cancer therapy, and it is important to elucidate the mechanisms controlling their various cellular effects. According to earlier studies, both syndecan-1 and syndecan-2 promote malignancy of HT-1080 human fibrosarcoma cells, by increasing the proliferation rate and the metastatic potential and migratory ability, respectively. To better understand their tumour promoter role in this cell line, syndecan expression levels were modulated in HT-1080 cells and the growth rate, chemotaxis and invasion capacity were studied. For in vivo testing, syndecan-1 overexpressing cells were also inoculated into mice. Overexpression of full length or truncated syndecan-1 lacking the entire ectodomain but containing the four juxtamembrane amino acids promoted proliferation and chemotaxis. These effects were accompanied by a marked increase in syndecan-2 protein expression. The pro-migratory and pro-proliferative effects of truncated syndecan-1 were not observable when syndecan-2 was silenced. Antisense silencing of syndecan-2, but not that of syndecan-1, inhibited cell migration. In vivo, both full length and truncated syndecan-1 increased tumour growth and metastatic rate. Based on our in vitro results, we conclude that the tumour promoter role of syndecan-1 observed in HT-1080 cells is independent of its ectodomain; however, in vivo the presence of the ectodomain further increases tumour proliferation. The enhanced migratory ability induced by syndecan-1 overexpression is mediated by syndecan-2. Overexpression of syndecan-1 also leads to activation of IGF1R and increased expression of Ets-1. These changes were not evident when syndecan-2 was overexpressed. These findings suggest the involvement of IGF1R and Ets-1 in the induction of syndecan-2 synthesis and stimulation of proliferation by syndecan-1. This is the first report demonstrating that syndecan-1 enhances malignancy of a mesenchymal tumour cell line, via induction of syndecan-2 expression

Structural and Functional Hierarchy in Photosynthetic Energy Conversion—from Molecules to Nanostructures

Basic principles of structural and functional requirements of photosynthetic energy conversion in hierarchically organized machineries are reviewed. Blueprints of photosynthesis, the energetic basis of virtually all life on Earth, can serve the basis for constructing artificial light energy-converting molecular devices. In photosynthetic organisms, the conversion of light energy into chemical energy takes places in highly organized fine-tunable systems with structural and functional hierarchy. The incident photons are absorbed by light-harvesting complexes, which funnel the excitation energy into reaction centre (RC) protein complexes containing redox-active chlorophyll molecules; the primary charge separations in the RCs are followed by vectorial transport of charges (electrons and protons) in the photosynthetic membrane. RCs possess properties that make their use in solar energy-converting and integrated optoelectronic systems feasible. Therefore, there is a large interest in many laboratories and in the industry toward their use in molecular devices. RCs have been bound to different carrier matrices, with their photophysical and photochemical activities largely retained in the nano-systems and with electronic connection to conducting surfaces. We show examples of RCs bound to carbon-based materials (functionalized and non-functionalized single- and multiwalled carbon nanotubes), transitional metal oxides (ITO) and conducting polymers and porous silicon and characterize their photochemical activities. Recently, we adapted several physical and chemical methods for binding RCs to different nanomaterials. It is generally found that the P(+)(Q(A)Q(B))(−) charge pair, which is formed after single saturating light excitation is stabilized after the attachment of the RCs to the nanostructures, which is followed by slow reorganization of the protein structure. Measuring the electric conductivity in a direct contact mode or in electrochemical cell indicates that there is an electronic interaction between the protein and the inorganic carrier matrices. This can be a basis of sensing element of bio-hybrid device for biosensor and/or optoelectronic applications

Tesofensine, a Novel Triple Monoamine Reuptake Inhibitor, Induces Appetite Suppression by Indirect Stimulation of α1 Adrenoceptor and Dopamine D1 Receptor Pathways in the Diet-Induced Obese Rat

Tesofensine is a novel monoamine reuptake inhibitor that inhibits both norepinephrine, 5-HT, and dopamine (DA) reuptake function. Tesofensine is currently in clinical development for the treatment of obesity, however, the pharmacological basis for its strong effect in obesity management is not clarified. Using a rat model of diet-induced obesity (DIO), we characterized the pharmacological mechanisms underlying the appetite suppressive effect of tesofensine. DIO rats treated with tesofensine (2.0 mg/kg, s.c.) for 16 days showed significantly lower body weights than vehicle-treated DIO rats, being reflected by a marked hypophagic response. Using an automatized food intake monitoring system during a 12 h nocturnal test period, tesofensine-induced hypophagia was investigated further by studying the acute interaction of a variety of monoamine receptor antagonists with tesofensine-induced hypophagia in the DIO rat. Tesofensine (0.5–3.0 mg/kg, s.c.) induced a dose-dependent and marked decline in food intake with an ED50 of 1.3 mg/kg. The hypophagic response of tesofensine (1.5 mg/kg, s.c.) was almost completely reversed by co-administration of prazosin (1.0 mg/kg, α1 adrenoceptor antagonist) and partially antagonized by co-administration of SCH23390 (0.03 mg/kg, DA D1 receptor antagonist). In contrast, tesofensine-induced hypophagia was not affected by RX821002 (0.3 mg/kg, α2 adrenoceptor antagonist), haloperidol (0.03 mg/kg, D2 receptor antagonist), NGB2904 (0.1 mg/kg, D3 receptor antagonist), or ritanserin (0.03 mg/kg, 5-HT2A/C receptor antagonist). Hence, the mechanism underlying the suppression of feeding by tesofensine in the obese rat is dependent on the drug's ability to indirectly stimulate α1 adrenoceptor and DA D1 receptor function

Highly flexible method for the fabrication of photonic crystal slabs based on the selective formation of porous silicon

10.1186/1556-276X-7-449Nanoscale Research Letters7