Should I stay or should I go?: Shedding of RPTPs in cancer cells switches signals from stabilizing cell-cell adhesion to driving cell migration

Dissolution of cell-cell adhesive contacts and increased cell-extracellular matrix adhesion are hallmarks of the migratory and invasive phenotype of cancer cells. These changes are facilitated by growth factor binding to receptor protein tyrosine kinases (RTKs). In normal cells, cell-cell adhesion molecules (CAMs), including some receptor protein tyrosine phosphatases (RPTPs), antagonize RTK signaling by promoting adhesion over migration. In cancer, RTK signaling is constitutive due to mutated or amplified RTKs, which leads to growth factor independence or autonomy. An alternative route for a tumor cell to achieve autonomy is to inactivate cell-cell CAMs such as RPTPs. RPTPs directly mediate cell adhesion and regulate both cadherin-dependent adhesion and signaling. In addition, RPTPs antagonize RTK signaling by dephosphorylating molecules activated following ligand binding. Both RPTPs and cadherins are downregulated in tumor cells by cleavage at the cell surface. This results in shedding of the extracellular, adhesive segment and displacement of the intracellular segment, altering its subcellular localization and access to substrates or binding partners. In this commentary we discuss the signals that are altered following RPTP and cadherin cleavage to promote cell migration. Tumor cells both step on the gas (RTKs) and disconnect the brakes (RPTPs and cadherins) during their invasive and metastatic journey.Key words: receptor protein tyrosine kinase, receptor-like protein tyrosine phosphatase, cadherins, cell adhesion, signal transduction, phospholipase C gamma, protein kinase C, catenins, IQGAP1 protein, regulated intramembrane proteolysis     

EFFECTS OF DIETARY SUPPLEMENTAL L-CARNITINE AND ASCORBIC ACID ON PERFORMANCE,CARCASS COMPOSITION AND PLASMA L-CARNITINE CONCENTRATION OF BROILER CHICKS REARED UNDER DIFFERENT TEMPERATURE

The present study was initiated to determine whether dietary supplemental L-carnitine and ascorbic acid affect growth performance, carcass yield and composition, abdominal fat and plasma L-carnitine concentration of broiler chicks reared under normal and high temperature. During the experiment, two temperature regimes were employed in two experimental rooms, which were identical but different in environmental temperature. The regimes were thermoneutral (20-22°C for 24 h) or recycling hot (34-36°C for 8 h and 20-22°C for 16 h). One-day-old broiler chicks (ROSS) were used in the experiment. A 2 x 2 x 2 factorial arrangement was employed with two levels (0 and 50 mg/kg) of supplemental L-carnitine and two levels (0 or 500 mg/kg) of supplemental ascorbic acid in drinking water under thermoneutral or high temperature regimes. Body weight gain was affected by high temperature. However, body weight gain was significantly improved in animals receiving supplemental L-carnitine, ascorbic acid or L-carnitine + ascorbic acid compared to animals receiving unsupplemented diet under high temperature. On the other hand, supplemental L-carnitine or L-carnitine + ascorbic acid reduced body weight gain under thermoneutral condition. Supplemental ascorbic acid significantly improved feed conversion efficiency, the improvement was relatively greater under high temperature. The L-carnitine content in the plasma was higher in the groups receiving supplemental L-carnitine and ascorbic acid under high temperature, while broilers fed supplemental L-carnitine and ascorbic acid had a decreased level of plasma L-carnitine concentration under normal temperature. It is concluded that dietary supplemental L-carnitine or L-carnitine + ascorbic acid may have positive effects on body weight gain, carcass weight under high temperature conditions.     

Biosynthesis of (2E,4E,6E)-5-acetoxymethyltetradeca-2,4,6-trienoic acid in Eremophila oppositifolia

Evidence is presented indicating that the triple conjugated branched chain fatty acid from Eremophila oppositifolia R.Br. arises by the acetate-malonate pathway with the side chain carbon atom originating from the S-methyl group of methionine.     

Potent trophic activity of spermidine supramolecular complexes in in vitro models

AIM:To test the growth-promoting activity of the polyamine spermidine bound to various polymeric compounds in supramolecular complexes.METHODS:A thiazolyl blue cell viability assay was used to determine the growth-promoting potency of spermidine-supramolecular complexes in a human skin fibroblast cell line exposed to spermidine and different spermidine-supramolecular complexes that were obtained by combining spermidine and polyanionic polymers or cyclodextrin.Reconstituted human vaginal epithelium was exposed to a specific spermidinesupramolecular complex,i.e.,spermidine-hyaluronan(HA)50,and cell proliferation was determined by Ki-67immunohistochemical detection.Transepithelial electrical resistance and histological analysis were also performed on reconstituted human vaginal epithelium to assess tissue integrity.RESULTS:The effect of spermidine and spermidinesupramolecular complexes was first tested in skin fi-broblasts.Spermidine displayed a reverse dose-related mode of activity with mmol/L growth inhibition,whereas 30%stimulation over basal levels was detected at mol/L and nmol/L levels.Novel spermidine-supramolecular complexes that formed between spermidine and polyanionic polymers,such as HA,alginate,and polymaleate,were then tested at variable spermidine concentrations and a fixed polymer level(0.1%w/v).Spermidine-supramolecular complexes stimulated the cell growth rate throughout the entire concentration range with maximal potency(up to 80%)at sub-mol/L levels.Similar results were obtained with spermidine-(-cyclodextrin),another type of spermidine-supramolecular complex.Moreover,the increased expression of Ki-67 in the reconstituted human vaginal epithelium exposed to spermidine-HA 50 showed that the mode of action behind the spermidine-supramolecular complexes was increased cell proliferation.Functional and morphological assessments of reconstituted human vaginal epithelium integrity did not show significant alterations after exposure to spermidine-HA,thus supporting its safety.CONCLUSION:Spermidine found in spermidine-supramolecular complexes displayed potentiated regenerative effects.Safety data on reconstituted human vaginal epithelium suggested that assessing spermidinesupramolecular complex efficacy in atrophic disorders is justified.     

The provision of supplementary fresh water improves the breeding success of the globally threatened Northern Bald Ibis Geronticus eremita

The Northern Bald Ibis Geronticus eremita is a globally threatened species with its main remaining world population breeding in an area of sea cliffs and coastal semi‐desert steppe near Agadir in southern Morocco. Between 1998 and 2002, we showed experimentally that the small‐scale provision of fresh water near the breeding colonies led to an increase in the productivity of the birds. The increase was greatest in years with low natural rainfall but was positive in all years tested. The supplementary fresh water appears to help buffer productivity against the impacts of low rainfall and its provision is now part of the ongoing conservation measures for this species.     

Quantitative co-occurrence of sesquiterpenes; a tool for elucidating their biosynthesis in Indian sandalwood, Santalum album

A chemotaxonomic approach was used to investigate biosynthetic relationships between heartwood sesquiterpenes in Indian sandalwood, Santalum album L. Strong, linear relationships exist between four structural classes of sesquiterpenes; alpha- and beta-santalenes and bergamotene; gamma- and beta-curcumene; beta-bisabolene and alpha-bisabolol and four unidentified sesquiterpenes. All samples within the heartwood yielded the same co-occurrence patterns, however wood from young trees tended to be more variable. It is proposed that the biosynthesis of each structural class of sesquiterpene in sandalwood oil is linked through common carbocation intermediates. Lack of co-occurrence between each structural class suggests that four separate cyclase enzymes may be operative. The biosynthesis of sandalwood oil sesquiterpenes is discussed with respect to these co-occurrence patterns. Extractable oil yield was correlated to heartwood content of each wood core and the oil composition did not vary significantly throughout the tree.     

Expression of low molecular weight heat-shock proteins and total antioxidant activity in the Mediterranean tree Quercus ilex L. in relation to seasonal and diurnal changes in physiological parameters

The total antioxidant activity (TAA) and the accumulation of small heat shock proteins (sHsps) were analysed under field conditions in Quercus ilex with regard to organ ontogeny and the physiological state of the plant. The results point toward the participation of sHsps and an increase of TAA in the general adaptation syndrome (GAS) of woody Mediterranean evergreens. In leaves and stems, there was a definite TAA seasonal pattern but no effect from diurnal variations or from the current stage of organ ontogeny. TAA was about twice as large in summer as in spring and winter and the hydrophilic antioxidant content was about 16 times greater than that of lipophilic antioxidants. The accumulation of sHsps in leaves also showed a seasonal pattern, but no effect from diurnal variations or from leaf ontogeny. In summer days, the sHsps content remained invariable even during the daylight hours in which the leaves were physiologically recovered. However, the accumulation of sHsps in stems did vary in relation to organ ontogeny. Old stems had a high accumulation of sHsps throughout the year, whereas in young stems, accumulation of sHsps was detected only in summer. This is probably due to a higher quantity of lignified and suberized tissues in the older stems. Using two‐dimensional immunodetection for leaves and stems, two sets of Hs protein species (17 and 10 kDa regions) were observed. In stems, there was an increase in 10 kDa proteins from winter to summer. These results are discussed and the possible role of the two types of polypeptides in the face of environmental and endogenous oxidative stress are considered.