OBJECTIVE: This study was to investigate the expression and significance of Integrins subunits in laryngeal squamous cell carcinoma (LSCC). METHOD: The expression of Integrins subunits was detected by cDNA microarray in 4 cases of primary LSCC tissues and corresponding adjacent normal tissues. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) were used to identify the different expression of Integrins subunits in 24 cases of primary LSCC tissues and corresponding adjacent normal tissues. RESULT: A cDNA microarray analysis revealed significant changes in the expression of Integrins subunits, with IntegrinalphaV, Integrinbeta8 being up-regulated and Integrinalpha8 being down-regulated. The result of RT-PCR was consistent with that of cDNA microarray. The mRNA levels of IntegrinalphaV and Integrinbeta8 were significantly higher in LSCC tissues than that in corresponding adjacent normal tissues (1.0131 +/- 0.4780 vs 0.7591 +/- 0.4678 for IntegrinalphaV, P<0.05, 1.7362 +/- 1.3849 vs 1.2267 +/- 0.9363 for Integrinbeta8, P<0.05). The mRNA levels of Integrinalpha8 were significantly lower in LSCC tissues than that in corresponding adjacent normal tissues (0.2646 +/- 0.2622 vs 0.5457 +/- 0.3827, P<0.05). CONCLUSION The expression of IntegrinalphaV, Integrinbeta8, Integrinalpha8 were significantly up-regulated or down-regulated in laryngeal squamous cell carcinoma, which may relate to tumorigenesis and development of laryngeal squamous cell carcinoma.
Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Humans ; Integrin alpha Chains ; genetics ; metabolism ; Integrin alphaV ; genetics ; metabolism ; Integrin beta Chains ; genetics ; metabolism ; Laryngeal Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; Neoplasm Proteins ; metabolism ; Neoplasm Staging

OBJECTIVETo study the expression of &beta;-integrin family members in children with T-cell acute lymphoblastic leukemia (T-ALL) and their significance.

METHODSQuantitative real-time PCR analyses were performed to assess the expression levels of &beta;-integrin family members in bone marrow samples from 22 children with newly-diagnosed T-ALL and 21 controls (16 children with non-malignant hematologic disease and 5 healthy donors with bone marrow transplantation). Jurkat cells were treated with integrin inhibitor arginine-glycine-aspartate (Arg-Gly-Asp, RGD) peptide. The cell viability and apoptosis rate were determined by CCK8 assay and flow cytometry respectively.

RESULTSThe mRNA levels of integrins &beta;, &beta;, and &beta;were significantly lower in children with T-ALL than in controls (P<0.05). In T-ALL patients, high integrin &beta;expression was associated with lower white blood cell counts (<100×10/L), minimal residual disease (MRD) positivity, and day 33 bone marrow negative remission (P<0.05). In T-ALL patients, higher integrin &beta;expression was associated with relapse of T-ALL (P<0.05). Based on survival curve analysis, higher integrin &beta;expression was related to lower event-free survival and overall survival rates. RGD peptide treatment inhibited the proliferation of Jurkat cells and increased their apoptosis rate (P<0.05).

CONCLUSIONS&beta;-Integrin may play a role in the occurrence and development of T-ALL by affecting cell proliferation and apoptosis. The expression of integrin &beta;5 is closely related to the risk of relapse of T-ALL. The expression of integrin &beta;3 is closely related the treatment response and prognosis of T-ALL.

Child ; Child, Preschool ; Female ; Humans ; Integrin beta Chains ; genetics ; physiology ; Jurkat Cells ; Male ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; etiology ; metabolism ; mortality ; RNA, Messenger ; analysis

OBJECTIVETo study the effect of &beta;8 expression on transforming growth factor &beta;1(TGF-&beta;1) activation in astrocytes with oxygen glucose deprivation (OGD).

METHODSAstrocytes were cultured and then subjected to OGD to generate hypoxia-ischemia (HI) model in vitro. Immunocytochemistry was used to detect the expression and distribution of &beta;8 in nomoxia cultured cells. &beta;8 protein expression was quantified by Western blot at 12 hours, 1 day and 2 days after OGD. Astrocytes and luciferase reporter cells (TMLC) were co-cultured. &beta;8 RNA interference system was established to specifically inhibit &beta;8 expression in cultured astrocytes. TGF-&beta;1 activation was then detected in the co-culture system.

RESULTS&beta;8 was mainly located in the cytoplasm and neurites of astrocytes. OGD resulted in increase of &beta;8 protein expression at 12 hours after reoxygenation in astrocytes, which was peaked at 1 day after reoxygenation. TGF-&beta;1 activation was in accordance with &beta;8 expression in astrocyte-TMLC co-culture system after reoxygenation. After the inhibition of &beta;8, TGF-&beta;1 activation was significantly reduced in all time points.

CONCLUSIONSThe highly expressed &beta;8 plays important roles in the regulation of TGF-&beta;1 activation in neonatal rats with hypoxic-ischemic brain damage.

Animals ; Astrocytes ; metabolism ; Female ; Glucose ; metabolism ; Hypoxia-Ischemia, Brain ; metabolism ; Integrin beta Chains ; physiology ; Male ; Oxygen ; metabolism ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; metabolism

This study inquired into the formation of the "overlapping growth" of hepatoma cells through quantitative characterization on the growth of hepatoma cells in situ by means of morphological observation, Image Tool computer analytic system, statistical analysis as well as the experimental methods of cell mechanics and biochemistry. The results were as follows: (1) The ability of hepatoma cells to regulate cell morphological deformation was better than that of hepatic cells; (2) While we were using micropipette aspiration technique to suck the "overlapping growth plaque" of hepatoma cells, the "overlapping growth plaque" fell off from the substrate, leaving a blank area; (3) Integrin expression of hepatoma cells was more obvious than that of hepatic cells; (4) Fibronectin (Fn) down-regulated the integrin expression in the hepatoma cells cultured on the Fn coated surface, enhanced the cells' adhesion ability and morphological stability, but reduced the formation and aggregation of the round cells. These results indicated (1) The so-called overlapping growing area was actually formed by many closely arrayed and piled round cells; (2) The production of round cells may be caused by integrin abnormal expression and the effect on the hepatoma cells adhesion stability; (3) The formation of "overlapping growth plaque" in hepatoma cells is related to the round cells' congregation induced by the high frequency morphological transformation.
Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Adhesion ; Cell Proliferation ; Fibronectins ; metabolism ; Humans ; Image Processing, Computer-Assisted ; Integrin beta Chains ; biosynthesis ; genetics ; Liver Neoplasms ; metabolism ; pathology ; Tumor Cells, Cultured

Epstein-Barr virus (EBV) establishes a latent infection in greater than 90% of the world's adult population and associates with various tumors. EBV primarily infects epithelial cells and B cell in vivo. Mechanism of EBV infection in B cells is known to involve binding of EBV glycoprotein gp350 to CD21 on B cell surface. Epithelial cells are infected with EBV even though most of epithelial cells do not express CD21. Recently, integrin alphavbeta5, alphavbeta6 and alphavbeta8 on epithelial cells were reported to facilitate EBV infection by interacting with gHgL complex. We examined the expression profile of integrins known to be expressed on epithelial cells. Integrin alphavbeta5 and alphavbeta6, but not alphavbeta8 were detected in a gastric epithelial cell line, AGS. We then tested whether siRNAs specific to beta6 can inhibit EBV infection of epithelial cells. One among the four tested siRNAs significantly reduced beta6 expression and suppressed transfer infection of EBV to AGS cells. Our data suggest that siRNAs to integrins might be useful to control EBV infection to epithelial cells.
Adult ; B-Lymphocytes ; Epithelial Cells ; Epstein-Barr Virus Infections ; Glycoproteins ; Herpesvirus 4, Human ; Humans ; Integrin beta Chains ; Integrins ; Receptors, Vitronectin ; RNA, Small Interfering

In order to study the roles of integrin beta6 in Foot-and-Mouth Disease Virus infection, pig integrin beta6 was firstly molecularly cloned from RNA of the tongue and lung of recovered pig infected experimentally with foot-and-mouth-disease virus (FMDV), and was compared with the beta6 gene of other animals available in GenBank at nucleotide and amino acid leves. GeneBank association number of the beta6 gene is EF432729. Pig integrin beta6 gene (2367bp) encodes a polypeptide of 788 amino acids consisting of 9 potential N-linked glycosylation sites, 3 Glycosaminoglycan attachment sites, a cGMP-dependent protein kinase phosphorylation site, 10 Protein kinase C phosphorylation sites, 2 EGF-like domains and 2 cysteine-rich regions. Pig integrin beta6 subunit has a 26-residue putative signal peptide, a 681-residue ectodomain, a 29-residue transmembrane domain, and a 52-residue cytoplasmic domain. 11 mutant nucleotides were found in beta6 gene coding region and 9 amino acids were changed. The nucleotide sequence similarity of integrin beta6 gene between rheses monkey, mouse, Norway rat, dog, guinea pig, human, bovine, sheep is 79.5%, 84.9%, 85.4%, 85.2%, 88.7%, 90.1%, 91.9% and 91.9%, and the amino acid sequence similarity is 93.5%, 88.2%, 88.5%, 88.3%, 91.0%, 92.8%, 93.3% and 93.4% respectively. This study will lay a foundation for understanding the interactions of FMDV with receptors.
Amino Acid Sequence ; Animals ; Base Sequence ; Cloning, Molecular ; DNA, Complementary ; Foot-and-Mouth Disease Virus ; pathogenicity ; Integrin beta Chains ; genetics ; metabolism ; Molecular Sequence Data ; Mutation ; Receptors, Virus ; genetics ; metabolism ; Sequence Analysis ; Swine ; genetics

OBJECTIVETo explore the molecular mechanism of the sensitivity of myocardial cell injury after severe hypoxia.

METHODSDifferential expression of the genes in rat myocardium and skeletal muscles after severe hypoxia for 6 hours was determined by DNA chip containing 4096 mice genes.

RESULTSThere were high expressions of 125 genes in skeletal muscles and 111 genes in myocardial cells after 6 hours of severe hypoxia. Among them, high expression genes in myocardial cells included those encoding apoptosis activator Mtd, complement C3, vascular cell adhesion molecule-1, integrin beta subunit and lipopolysaccharide binding proteins (LBP).

CONCLUSIONActivation of apoptosis of myocardial cells and inflammatory mediators played important roles in myocardial cell injury after 6-hour severe hypoxia.

Animals ; Cells, Cultured ; Complement C3 ; metabolism ; Gene Expression Profiling ; Hypoxia ; metabolism ; Integrin beta Chains ; metabolism ; Mice ; Muscle, Skeletal ; metabolism ; pathology ; Myocytes, Cardiac ; metabolism ; pathology ; Oligonucleotide Array Sequence Analysis ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; RNA, Messenger ; metabolism ; Rats ; Vascular Cell Adhesion Molecule-1 ; metabolism

OBJECTIVETo investigate the effect of baicalein on proliferation and migration of multiple myeloma (MM) cell lines and its molecular mechanism.

METHODSThe MM cell line RPMI-8226 and U266 cells were used as the model, and treated with different concentration and time of baicalein the effect of baicalein on the MM cells proliferation was assessed by MTT assay. With or without baicalein or Interleukin-6 (IL-6) treatment, the &beta;-catenin protein level was analyzed by immunofluorescence assay and western blot assay and mRNA levels of &beta;-catenin, c-myc, cyclin D1 and integrin 7 gene by RT-PCR. Transwell chamber migration assay was used to detect the cells migration ability with different concentration of baicalein cultured.

RESULTSBaicalein inhibited the MM cell line RPMI 8226 and U266 cell proliferation in a dose- and time-dependent manner. It simultaneously inhibited &beta;-catenin protein level to resist the effect of IL-6 on inducing MM cell proliferation, and resulted in decrease of &beta;-catenin, c-myc, cyclinD1 and integrin &beta;7 mRNA levels. Baicalein also decreased migration ability of MM cells in a dose-dependent manner by SDF-1.

CONCLUSIONBaicalein can inhibit MM cells proliferation and migration, and its molecular mechanisms are associated with inhibition of proliferation related genes &beta;-catenin, c-myc, cyclin D1 and integrin &beta;7 expression.

Antigens, CD ; metabolism ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Cyclin D1 ; metabolism ; Flavanones ; pharmacology ; Humans ; Integrin alpha Chains ; metabolism ; Interleukin-6 ; pharmacology ; Multiple Myeloma ; metabolism ; pathology ; Proto-Oncogene Proteins c-myc ; metabolism ; RNA, Messenger ; genetics ; beta Catenin ; metabolism

OBJECTIVE: To comparatively investigate the expression of several integrins in specimens of human bone metastases and degenerative bone tissue. METHODS: Degenerative cancellous tissue was obtained from a sample of human degenerative spine. Thirteen human specimens were obtained from metastatic spine tumors, whose primary cancer was colon cancer (n=3), hepatocellular cancer (n=3), lung cancer (n=4), and breast cancer (n=3). The expression of vimentin and integrins alphav, beta1, and beta3 was assessed in metastatic and degenerative specimens by immunohistochemistry and real-time reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS: Immunohistochemical staining showed that vimentin and integrin alphav was broadly expressed in all tissues examined. By contrast, integrin beta1 was weakly expressed only in 38.4% (5/13) of tissues. Integrin beta3 was consistently negative in all cases examined. qRT-PCR analysis showed that vimentin gene expression was higher in all metastatic specimens, as compared to degenerative bone. The gene expression of integrin alphav in breast specimen was significantly higher than others (p=0.045). The gene expression of integrin beta1 was also higher in all metastatic specimens than in degenerative bone tissue. The gene expression of integrin beta3 was variable. CONCLUSION: Spinal metastatic tumors have mesenchymal characteristics such as increased expression of vimentin. The increased expression of integrin alphav and beta1 in spine metastatic tumors suggests that adhesive molecules such as integrin may have implications for the prevention of spine metastasis.
Adhesives ; Antigens, CD29 ; Bone and Bones ; Breast ; Breast Neoplasms ; Colonic Neoplasms ; Gene Expression ; Humans ; Immunohistochemistry ; Integrin alphaV ; Integrin beta3 ; Integrins* ; Liver Neoplasms ; Lung Neoplasms ; Neoplasm Metastasis ; Spine* ; Vimentin*

INTRODUCTION: The pathophysiology of PIH remains unclear. Recently, placental abnormalitiesare stressed as a possible cause of PIH. Abnormal shallow invasion of trophoblasts, confinedto decidua, without involving myometrium is believed to result in reduced uteroplacentalperfusion, endothelial injury, and activation of coagulation cascade system. Integrin, one of theadhesive membrane proteins, is expected to be related to the regulation of trophoblasts invasion. PURPOSE: The purpose of this study is to investigate the expression of adhesion moleculesin placenta and the correlation between uterine artery Doppler findings and integrinexpressions in the placentas of PIH patients. SUBJECTS: Thirty-six cases of severe PIH patients were enrolled in the study with 10number of normal control pregnant women. The integrin subunit expressions withimmunohistochemical staining were observed in floating villi, maternal-side cytotropholbasts, andfetal-side cytotrophoblasts. Uterine artery Doppler study was also performed, and the S/Dratio was evaluated. Abnormal Doppler findings was defined as S/D ratio>or=2.6. RESULTS: Cytoplasmic staining of villi and placental bed cytotrophoblast for theintegrin alpha1 subunit in PIH specimen was weaker than those in normal controls. Theexpression of integrin beta1 subunit was negative for both controls and PIH group. Thepositive cytoplasmic stain was observed among PIH placenta in contrast to normal control inwhich the expression of integrin beta4 subunit was not detected. The expression of alpha v beta3 introphoblast with PIH was positive staining, but not in control group. Uterine artery Dopplervelocimetry was performed in 25 cases with PIH. Trace(+/-) or - staining of integrin alpha1 subunit were observed in 60.0% of abnormal S/D(>or=2.6) group, 20.0% of normal S/Dratio group patients, respectively. Trace or + staining of integrin beta4 subunit were observedin 50.0% of abnormal S/D group and 6.7% of normal S/D group and this is in statisticallysignificant. Trace or + staining of integrin alpha v beta3 subunit were observed 70.0% ofabnormal S/D group and 26.7% of normal S/D group, and this statistically significant. CONCLUSION: In PIH the abnormality in the invasion of cytotrophoblats results inabnormal integrin subunit expression, but it is also correlated to the abnormal uterine arteryDoppler velocimetry which shows a S/D ratio of greater than 2.6. Thus, the uterine arteryDoppler velocimetry reflects abnormal placentation.
Animals ; Antigens, CD29 ; Cytoplasm ; Decidua ; Female ; Humans ; Hypertension, Pregnancy-Induced* ; Integrin alpha1 ; Integrin alphaV ; Integrin beta4 ; Integrins ; Membrane Proteins ; Mice ; Myometrium ; Placenta* ; Placentation ; Pregnancy ; Pregnant Women ; Rheology* ; Trophoblasts ; Uterine Artery*