Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Integrin alphaV”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 613 records · Page 34Linked to original sources
PubMed1998

Protein phosphatase 1 delta is associated with focal adhesions.

In all mammalian cells protein phosphatase-1 (PP1) exists in three isoforms, defined as alpha, gamma 1 and delta. Immunofluorescence studies with isoform-specific antibodies indicated that delta, but not alpha or gamma 1, is enriched at focal adhesions in HeLa cells, fibroblasts, endothelial cells and keratinocytes. This was confirmed also by interference reflection microscopy, which indicated that PP1 delta was in areas of tight adhesion of the membrane to the extracellular matrix at sites where the microfilament cytoskeleton is organized. In all the cell types so far considered the PP1 delta in focal adhesions represented only a small aliquot of the total PP1 delta, which was predominantly localized to the nucleus. The association of PP1 delta to focal adhesions was confirmed by the co-immunoprecipitation of PP1 delta with the focal adhesion kinase pp125FAK and with the alpha v integrin. Comparison between the amount of PP1 delta associated with focal adhesion proteins and that of PP1 delta recovered in an anti-PP1 delta immunoprecipitate confirmed that only a minor amount of the enzyme was associated with the focal adhesions. Since some focal adhesion proteins are phosphorylated on Ser/Thr, it is likely that PP1 delta may be involved in the regulation of focal adhesion functions and particularly in the signaling pathway generated by cell-substratum adhesion.

3T3 Cells↗
PubMed1999

Growth and differentiation of the vascular smooth muscle and endothelial cells cultured on fluorine ion-implanted polystyrene.

The rat vascular (SMCs) and bovine endothelial cells (BECs) were cultured on conventional or fluorine ion-implanted polystyrene (5 x 10(12) and 5 x 10(14) fluorine ions/cm2). The cells grown on the implanted growth supports showed better adherence, higher volume and higher total protein content. The immunocytochemical analysis revealed that SMCs contained more of the cytoskeletal vimentin and the vascular SMC-specific alpha-actin as well as several cell adhesion-mediating molecules (vinculin, talin, alpha(v)-integrin and ICAM-1). In BECs, only the content of vimentin and talin increased, while expression of ICAM-1 was unchanged. The data suggest that cells on the ion implanted polymers could be more viable and that increased expression of some adhesion molecules mediating interactions with the host immune system is cell type-dependent.

Actins↗
PubMed1999

Different responsiveness of male and female rat aortic smooth muscle cells (SMCs) to repeated passaging in culture.

The smooth muscle cell (SMC) cultures were prepared from the aorta of male and female 8-week-old rats and used at passage 5-7 or 40-45. On day 1, low-passaged cells of both sex groups adhered to growth supports at similar numbers while after repeated passaging the adherence of female-derived cells was higher. These cells had also higher total protein content and contained more of the SMC specific alpha-actin, vimentin and alpha(v) integrins. Compared to the male type of cultures, the high passaged cells of female origin cycled at a slower rate and were undergoing massive polyploidization. Male-derived cells remained of the same morphology, ploidy and the differentiation status at all passages. Their passage response consisted mainly in faster cycling and growth to higher population densities. The data could be of importance for explanation of different incidence of hyperplastic vascular diseases in males and females.

Actins↗
PubMed2001

The "early' CD4+CD8+ stage of thymocte differentiation hallmarks the end of a strong positive correlation between extracellular matrix receptor expression and protein tyrosine phosphorylation.

We used irradiation-induced thymic regression/reconstitution to study phosphotyrosine (PTyr) levels and expression of extracellular matrix receptors in thymocyte subsets by flow cytometry. High PTyr levels (PTyr(hi)) characterized cells from the CD4-CD8-(DN)CD25in/hi to the "early" CD4-CD8+(DP)CD25- stage. Correlation indexes (R) between the percentages of these PTyrhi cells and cells with up-regulated expression of alpha4 integrin (alpha4hi) were strongly positive (R= 0.91, P= 0.002, for DN; R= 0.98, P= 0.0001 for DP). At the "early" DP stage, R between PTyrhi cells and cells with up-regulated expression of alpha5 integrin and L-selectin (alpha5hi and L-sel(hi)) also rendered strongly positive (R>0.95, p<0.0003). "Late" expanding DP cells exhibited intermediate PTyr levels (PTyr(in)), associated with a down-regulation of the adhesion receptors assessed. Triple-labeling suggested that in most early CD3-/lo cells, alpha4hi and alpha5hi, but not L-sel(hi) expression preceded a PTyr(hi) content. CD3in/hi-enriched CD8+ cells were also PTyr(hi), but conversely to the immature ones exhibited a tendency for a negative R between PTyr(hi) and alpha4hi (R = -0.93, P = 0.067, n= 4) or alpha5hi cells (R = -0.77, P = 0.23, n = 4). CD4+ cells were either PTyr(hi) or PTyr(in), exhibiting a tendency for a positive R (R = 0.59, P = 0.124, n= 8) between PTyr(hi) and L-sel(hi) cells only. In conclusion, our results associate an up-regulation of alpha4 and alpha5 chains expression with PTyr(hi) levels and, as elsewhere published, with increased adhesion to fibronectin up to the "early" DP stage, but not afterwards.

Animals↗
PubMed2001

Fiber knob modifications overcome low, heterogeneous expression of the coxsackievirus-adenovirus receptor that limits adenovirus gene transfer and oncolysis for human rhabdomyosarcoma cells.

Exploiting the lytic life cycle of viruses has gained recent attention as an anticancer strategy (oncolysis). To explore the utility of adenovirus (Ad)-mediated oncolysis for rhabdomyosarcoma (RMS), we tested RMS cell lines for Ad gene transduction and infection. RMS cells were variably transduced by Ad. Compared with control cells, RMS cells were less sensitive or even resistant to oncolysis by wild-type virus. RMS cells expressed the Ad internalization receptors, alpha(v) integrins, but had low or undetectable expression of the major attachment receptor, coxsackievirus-Ad receptor (CAR). Mutant Ads with ablated CAR binding exhibited only 5-20% of transgene expression in RMS cells seen with a wild-type vector, suggesting that residual or heterogeneous CAR expression mediated the little transduction that was detectable. Immunohistochemical analysis of archived clinical specimens showed little detectable CAR expression in five embryonal and eight alveolar RMS tumors. Stable transduction of the cDNA for CAR enabled both efficient Ad gene transfer and oncolysis for otherwise resistant RMS cells, suggesting that poor CAR expression is the limiting feature. Gene transfer to RMS cells was increased >2 logs using Ads engineered with modified fiber knobs containing either an integrin-binding RGD peptide or a polylysine peptide in the exposed HI loop. The RGD modification enabled increased oncolysis for RMS cells by a conditionally replicative Ad, Ad delta24RGD, harboring a retinoblastoma-binding mutation in the E1A gene. Thus, the development of replication-competent vectors targeted to cell surface receptors other than CAR is critical to advance the use of Ad for treating RMS.

Adenoviridae↗
PubMed2001

Enhanced adenovirus transgene expression in malignant cells treated with the histone deacetylase inhibitor FR901228.

The presence of coxsackie and adenovirus receptor (CAR) and alpha(v) integrin on cell surfaces is required for efficient adenovirus infection. Treatment of cells with the histone deacetylase inhibitor FR901228 (depsipeptide) increased CAR and alpha(v) integrin RNA levels in six cancer cell lines. Sodium butyrate and trichostatin A, other histone deacetylase inhibitors, caused similar increases. Cells treated with FR901228 prior to infection had a 4-10-fold increase in transgene expression from a beta-galactosidase-expressing adenoviral vector. These studies suggest that FR901228 increases the efficiency of adenoviral transgene expression and may be useful in cancer gene therapy.

Adenoviridae↗
PubMedDate not supplied

Antisense to integrin alpha v inhibits growth and induces apoptosis in medulloblastoma cells.

BACKGROUND: Integrin alpha v promotes brain microvessel endothelium survival, yet its role in brain tumor cells is unknown. MATERIALS AND METHODS: Alpha v synthesis in medulloblastoma cells Daoy, D341Med, and D283Med, was inhibited with antisense oligonucleotides (ASODN) to test the effect on growth and survivaL RESULTS: ASODN reduced alpha v surface expression 75% in a dose- and time-dependent manner (2 microM, 72 hours). Alpha v-deficient cells grown with vitronectin demonstrated reduced cell spreading, G0-G1 growth arrest, decreased proliferation and increased apoptosis compared to controls or alpha v-deficient cells grown with collagen. Furthermore, insulin-like growth factor-I (IGF-I) suboptimally stimulated proliferation and survival of alpha v-deficient cells, suggesting that alpha v-IGF-I interactions potentiate medulloblastoma growth. Finally, treatment with alpha v-blocking antibody induced caspase-8 and caspase-3 expression, while apoptosis of alpha v-deficient cells was associated only with increased caspase-3. CONCLUSION: Alpha v integrin supports medulloblastoma growth by activating adhesion-dependent and -independent survival pathways and thus may serve as a novel therapeutic target in this tumor.

Antigens, CD↗
PubMedDate not supplied

Integrin alpha v, c-erbB2 and DNA ploidy in lung metastases from colorectal cancer.

BACKGROUND/AIMS: We analyzed integrin alpha v and c-erbB2 expression and DNA ploidy in primary tumors and pulmonary metastases from colorectal carcinoma. METHODOLOGY: Fifty primary tumors and 21 lung metastases were examined for immunohistochemical detection of integrin alpha v, c-erbB2 and DNA ploidy. RESULTS: In integrin alpha v-positive tumors, integrin alpha v was strongly recognized in the cytoplasm of colorectal carcinoma. In total cases, in a multivariate model using logistic stepwise regression analysis, venous invasion was significantly and independently related to lung metastasis in patients who underwent curative resection. Integrin alpha v, c-erbB2 and DNA ploidy in primary tumors were not predictable for lung metastasis. On the other hand, in the 21 patients with lung metastases, integrin alpha v overexpression was identified in 52.4% (11/21) of primary tumors and in 85.7% (18/21) of lung metastases, respectively. The positive ratio was significantly higher in lung metastases than in primary tumors (p < 0.05). There was no significant difference between primary tumors and lung metastases in DNA ploidy or c-erbB2 expression. CONCLUSIONS: Integrin alpha v might be one of the important signals for formation of lung metastases from colorectal cancer as a late event.

Adenocarcinoma↗
PubMed2003

Coxsackievirus adenovirus receptor expression predicts the efficiency of adenoviral gene transfer into non-small cell lung cancer xenografts.

PURPOSE: Current paradigms postulate that inefficient adenoviral (Ad) gene transfer is a consequence of poor Coxsackievirus adenovirus receptor (CAR) expression in tumors in vivo. To test whether exuberant CAR expression alone is sufficient to mediate efficient Ad gene transfer, we compared Ad gene transfer efficiency in a panel of non-small cell lung cancer (NSCLC) cell model systems in which we systematically measured CAR expression in vitro and in vivo. EXPERIMENTAL DESIGN: NSCLC cells were selected for study on the basis of (a) differences in Ad transduction, (b) identical requirements for growth in vitro, (c) capacity to grow as xenografts in immunocompromised mice, and (d) similar amounts of alpha(v) integrin expression as measured by flow cytometry. CAR expression and Ad transduction profiles of these NSCLC cells were generated in vitro and in vivo. RESULTS: Ad transduction efficiency of NSCLC cells in vitro can be directly related to CAR expression at both the mRNA and protein level. CAR expression in vitro favorably predicts a comparable pattern of expression in transplanted NSCLC xenografts in vivo. Xenografts generated from NSCLC cells exhibiting increased CAR expression showed evidence of higher Ad gene transfer, although the efficiency of transduction was reduced compared with in vitro measurements. Thus, in NSCLC cells with high basal expression of CAR, Ad vector doses that enabled uniform transduction in vitro achieve a gene transfer efficiency ranging from 10% to 70% after a single intratumoral injection in the xenografts. CONCLUSIONS: These studies indicate CAR expression is predictive for more efficient gene transfer into NSCLC cells in vitro and in vivo but is not sufficient to achieve uniform transduction by Group C Ad vectors in vivo.

Adenoviridae↗
PubMed2003

The histone deacetylase inhibitor FK228 preferentially enhances adenovirus transgene expression in malignant cells.

PURPOSE: Efficient adenovirus infection requires coxsackie-adenovirus receptor (CAR) and alpha(v) integrin. Whereas many malignant cells express these proteins poorly, normal tissues, especially liver, express high levels and are susceptible to adenovirus infection. Our previous studies showed that treatment of cancer cell lines with low concentrations of the histone deacetylase inhibitor FK228 (FR901228, depsipeptide), a drug in Phase II clinical trials, before infection was associated with an increase in adenovirus transgene expression. The purpose of these studies was to analyze the effects of FK228 on cultured normal human cells before initiating animal studies. EXPERIMENTAL DESIGN: Cancer and normal cells from the corresponding tissue were treated with FK228 and analyzed for the proteins needed for infection and the infection efficiency. RESULTS: Treatment of cancer cell lines with 1 ng/ml FK228 increased CAR RNA, alpha(v) integrin RNA, and histone H3 acetylation levels, and was associated with a 4-10-fold increase in the number of infected cells expressing the transgene. Similar treatment of normal human mammary epithelial cells, renal proximal tubule epithelial cells, and hepatocytes had little effect. The insensitivity of cultured normal cells may be explained, in part, by expression of the drug efflux pump P-glycoprotein, because addition of the P-glycoprotein inhibitor XR9576 (tariquidar) with FK228 resulted in increased histone acetylation and CAR expression. CONCLUSION: These studies suggest that low concentrations of FK228 preferentially increase the efficiency of adenoviral transgene expression in cancer cells compared with cultured normal cells from the corresponding tissue and may increase the efficiency of adenovirus therapies in vivo.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Circulating endothelial microparticles in patients with acute myocardial infarction.

BACKGROUND: Circulating endothelial microparticles (EMPs), the small vesicles released from altered endothelial cells, have been established as markers of endothelial injury. The elevated count of EMPs has been described in different conditions involving endothelial injury, including acute myocardial infarction (AMI). AIM: To assess the presence of EMP in patients with acute MI in relation to early clinical outcome and coronary angiography results. MATERIALS AND METHODS: EMPs counts were determined in 66 patients pts (23 women, 43 men) with documented ST elevation AMI and in 10 control patients with no evidence of coronary artery disease. All pts with AMI underwent coronary angiography with attempted primary angioplasty. EMPs were assayed by flow cytometry in platelet-poor plasma with combinations of fluorescent antibodies (anti CD31, -51, -42) allowing distinction of EMPs from platelet microparticles. Clinical and angiography results were compared with EMP levels. RESULTS: Three kinds of EMPs were measured: CD31+, CD51+ and CD31+/51+. The percentage of EMPs CD31+/CD51 was significantly (p=0,042) higher in patients with AMI in comparison with control subjects. However, a marker, which distinguished both groups the most, was the level of EMPs CD51+. It was significantly (p=0,024) higher in pts with AMI than in control pts. The levels of CD31+ were similar in both groups. There was no correlation between EMP levels, clinical and angiography results. CONCLUSION: The presence of circulating EMPs provides direct evidence of endothelial injury in AMI. The clinical and practical value of these results, however, needs further exploration.

Adult↗
PubMed2005

Hyaluronan and sulphated hyaluronan micropatterns: effect of chemical and topographic cues on lymphatic endothelial cell alignment and proliferation.

While tissue engineered blood vessels have entered surgical practice, the construction of artificial lymphatic vessels has never been attempted due to the small dimensions and fragility of lymphatic vessels. A possible alternative would be to obtain a new growth of interrupted lymphatic vessels. We have previously reported that lymphatic endothelial cells align when cultured on striped micropatterns of hyaluronan (Hyal) and aminosilanized glass. We here report a comparative study in which lymphatic endothelial cells have been plated on micropatterns with stripes of different width and height obtained by the photoimmobilization of Hyal and its sulphated derivative (HyalS) on aminosilanized glass to verify whether their response correlated with surface-chemistry andlor topography. On Hyal micropatterns, cells adhered to aminosilanized glass, avoiding Hyal stripes and molding their shape in accordance to the micropattern topography. Stress fibers, integrins and focal adhesion kinase organized accordingly. HyalS micropatterns with the same topography were unable to guide cell response, cells randomly adhered to HyalS and glass stripes, and polarization was attained only by increasing stripe height. These data indicate that surface chemistry is the main cue responsible for lymphatic endothelial cell guidance. When surface chemistry of stripes promotes cell adhesion as well as that of the substrate, topographical parameters become prevalent. Micropatterns with defined chemical and topographical properties may contribute to the design of new platforms for controlled cell growth in tissue engineering of lymphatic vessels.

Actins↗
PubMed2006

Molecular changes in the gingival epithelium associated with necrotizing ulcerative periodontitis: a case report.

A case of necrotizing ulcerative periodontitis (NUP), the most severe inflammatory periodontal disorder caused by plaque bacteria, is shown. Clinically, the gingiva showed distinct signs of ulceration, and radiography revealed horizontal bone loss. Indirect immunofluorescence, carried out on frozen sections of tissue specimens obtained from the NUP lesion, exhibited clear expression of atypical keratin K19, particularly in basal cells, when compared to noninflamed gingiva. Moreover, NUP tissue showed extensive intraepithelial abundance for the basement membrane component laminin-1/10 and the extracellular matrix molecule tenascin. Strong expression of integrin subunit alphav and matrix metalloproteinase-13 in conjunction with interleukin 1-beta further discriminated NUP gingival epithelium from normal tissue. The results suggest that NUP is associated with changes in the expression and topography of the analyzed molecules in the gingival epithelium, which in turn may reflect the fast progression of the disease.

Adult↗
PubMed2006

[Construction of a recombinant adenoviral vector carrying integrin-alpha v and the influence of integrin-alpha on the adhesion characteristics of SMMC-7721 cells].

OBJECTIVE: To establish human integrin-alpha v adenovirus expressed in human liver cancer SMMC-7721 cells and analyze the characteristics of integrin-alpha adhesion to liver cancer cells. METHODS: Human integrin-alpha v cDNA was cloned into the plasmid pAdTrack-CMV. Then, pAdTrack-integrin-alpha v was cotransformed with adenoviral backbone vector into E. coli strain BJ5183. The recombinant adenoviral plasmid was identified by restriction analysis with Pac I and transfected into HEK-293A cells to package and amplify recombinant adenovirus particles. Western blot showed that integrin-alpha v gene was exactly transcript and expressed in SMMC-7721 cells. Twenty four hours after transfection, the effect of integrin-alpha on adhesion of SMMC-7721 cells was detected by adhesion experiment. RESULTS: Recombinant adenovirus vector of integrin-alpha v gene was successfully constructed and high titers of recombinant adenovirus was obtained. Adhesion cell count was significantly higher in integrin-alpha v transfected cells than in untransfected and Ad-null-transfected cells (P<0.01). CONCLUSION: Over expression of integrin-alpha v promotes adhesion of SMMC-7721 cells, is an important molecular mechanism of tumor metastasis.

Adenoviridae↗
PubMedDate not supplied

A DNA motif present in alpha V integrin promoter exhibits dual binding preference to distinct transcription factors.

Antisense inhibition of the RelA subunit but not the NFKB1 subunit of NK-kappa B transcription factor results in a block of cellular adhesion and inhibition of tumor cell growth in vitro and in vivo. Studies aimed at dissecting the molecular mechanism of antisense relA action led to our identification of a kappa B-like motif present in aV integrin promoter. The alpha V/kappa B motif is closely related to RelA/c-Rel-binding sequences, such as 65-2 and TF-1. However, unlike these two kappa Blike motifs, the alpha V/kappa B motif detected a nuclear Sp1 activity distinct from kappa B activity, which was subsequently confirmed to be derived from Sp1. In comparison to the conventional GC box-containing Sp1 motif, the alpha V/kappa B motif also binds in vitro to c-Rel and RelA but not to NFKB1. Antisense inhibition of RelA inhibited the alpha V/kappa B activity. Direct in vivo competition of alpha V/kappa B-binding activity by a decoy approach also resulted in inhibition of alpha V/kappa B activity in intact cells. A variant of the alpha V/kappa B motif was found to retain the dual ability to detect Sp1 and the NF-kappa B complex in the nuclear and cytoplasmic extracts. Such dual interacting ability of a DNA motif offers yet another way of gene regulation in vivo and hence can affect cellular growth. Our results identify alpha V integrin as one of the molecular targets for relA/NF-kappa B and may explain growth inhibition by antisense relA.

Animals↗
PubMed1997

Expression and function of endothelial cell alpha v integrin receptors in wound-induced human angiogenesis in human skin/SCID mice chimeras.

Accumulating evidence indicates that endothelial cell integrins that bind to the matrix proteins associated with inflammation and wound healing are involved in the process of angiogenesis. The integrins containing the alpha v subunit appear to be particularly important. To study the involvement of these receptors in human angiogenesis, a model of wound-associated human angiogenesis was established in human skin transplanted onto severe combined immunodeficient (SCID) mice. Using this model, we studied the expression of several alpha v integrins and tested the hypothesis that blockage of the alpha v beta 3 integrin would inhibit human angiogenesis during human wound healing. These studies revealed that the alpha v beta 3, alpha v beta 5, and alpha v beta 6 integrins are up-regulated briefly during wound angiogenesis with different patterns of expression and that inhibition of the alpha v beta 3 integrin blocked new vessel formation during human wound healing.

Animals↗