Cell adhesion receptors and cancer

Cell-to-cell and cell-to-extracellular matrix (ECM) interactions in the functions of cell adhesion and signal transduction are important in global control of cell phenotypes and cell behavior and are crucial for maintenance of homeostasis and structural/functional stabilization of tissues and organs. Cell adhesion receptors are recognized as the molecular basis of cell adhesion. Cadherin and lntegrin are widely expressed adhesion receptors in most tissues. They are transmembrane glycoproteins which,through their cytoplasmic domain, bind to many proteins at the inner surface of cell membrane to form molecule-linkage complexes and then connect with the cytoskeleton. Through cell adhesion receptors a network functioning as cell adhesion and signal transduction is organized between tissue cells and cellECM. In this regard cell adhesion receptors play an important role in regulation of morphogenesis, cellcell recognition, cell migration, cell sorting and the determination of cell’s fate in development.

Cell surface clustering of Cadherin adhesion complex induced by antibody coated beads

Cadherin receptors mediate cell-cell adhesion, signal transduction and assembly of cytoskeletons. How a single transmembrane molecule Cadherin can be involved in multiple functions through modulating its binding activities with many membrane adhesion molecules and cytoskeletal components is an unanswered question which can be elucidated by clues from bead experiments. Human lung cells expressing N-Cadherin were examined. After co-incubation with anti-N-Cadherin monoclonal antibody coated beads, cell surface clustering of N-Cadherin was induced. Immunofluorescent detection demonstrated that in addition to Cadherin, β-Catenin, α-Catenin, a-Actinin and Actin fluorescence also aggregated respectively at the membrane site of bead attachment. Myosin heavy chain (MHC), another major component of Actin cytoskeleton, did not aggregate at the membrane site of bead attachment. Adhesion unrelated protein Con A and polylysine conjugated beads did not induce the clustering of adhesion molecules. It is indicated

Synthesis and Structure of Tetrahydro-4,7- ethanoisobenzofuran-1,3-dione Derivative

(1R,2R,3S,4R,7R)-7-Isopropyl-6-methylbicyclo[2.2.2]oct-5-ene-2,3-dicarboxylic acid anhydride(tetrahydro-4,7-ethanoisobenzofuran-1,3-dione derivative)adduct 2 was prepared via the isomerization ofα-pinene andβ-pinene in turpentine followed by the Diels-Alder cycloaddition with maleic anhydride in the presence of phosphoric acid/iodine catalysis.The molecular structure of adduct 2 was characterized by IR,1H NMR,13C NMR,1H-1H COSY,DEPT,HSQC,HMBC,2D NOESY and MS spectra.The single crystal X-ray crystallographic analysis of adduct 2 was performed,and the X-ray powder diffractive spectrum of the sample adduct 2 is consistent with the diffractive spectrum calculated from the single crystal data.Therefore the structure and stereochemistry of adduct 2 was established based on extensive spectral data and single crystal X-ray analysis.

Synthesis and DNA Cleavage Properties of Triazacrown Derivatives

New metal-free DNA cleaving reagent 1,1,4,7-triazacrown(TACN)both with aminoethyl,hydroxyethyl side arms and a planar anthraquinone linked by an alkyl(1,6-hexamethylene)spacer has been synthesized and characterized by NMR and MS spectrometry.For comparison,the corresponding aminoethyl,hydroxyethyl triazacrown derivative 2 without the anthraquinone has also been synthesized.DNA-binding properties via fluorescence and CD spectroscopy indicate that the binding affinity of 1 with DNA is much stronger than that of 2.Agarose gel electrophoresis was used to assess plasmid pUC19 DNA cleavage.Kinetic data of DNA cleavage promoted by 1,2 and parent triazacrown(TACN)3 under physiological condition give the 15-fold and 234-fold rate acceleration of compound 1 over 2 and parent triazacrown 3.Radical scavenger inhibition study suggests that DNA cleavage promoted by 1 may be a non-oxidative pathway through the transphosphorylation and then hydrolysis.The dramatic rate acceleration is due not only to the anthraquinone moiety of compound 1 intercalating into DNA base pairs via stacking interaction,but also the cooperative catalysis of the nucleophilic hydroxyl and the electrophilic ammonium group for the cleavage of phosphodiester of DNA.

The expression of N-cadherin/catenins/actin complex in human lung normal and carcinoma cells

The difference between human normal and carcinoma lung cells was studied with regard to the protein expression level and localization of the cadherin/catenin/actin complex. Results demonstrated that normal lung cell RF expressed high levels of N-cadherin, β-catenin, α-catenin. These 3 proteins were colocalized at AJs and their submembrane adhesion plaques where they link the Rho-phalloidin-positive actin stress fibers, indicating the existence of N-cadherin/catenin/actin complexes at the AJs. Aberrant expression of AJ proteins and the actin cytoskelecton in carcinoma PG cells was observed: (1) inhibition of N-cadherin and to a degree of inhibition of α-catenin protein expression; (2) varied protein modification of β-catenin in cytoplasm soluble fraction and altered distribution of immunofluorescence: majorly in the cytoplasm and minorly on the membrane; (3) disassembly of actin stress fibers and formation of actin bodies in the cytoplasm. The data suggest that inhibited expression of AJ proteins is correlated with the disruption of the AJ complexes and the actin cytoskeleton in carcinoma PG cells, and responsible for its metastasis behaviors.