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N I Kozlova

Publications and source records attributed to N I Kozlova.

17 recordsLinked to original sources
PubMed2006

The role of beta1 integrin subfamily in anchorage-dependent apoptosis of breast carcinoma cells differing in multidrug resistance.

Integrin expression was investigated in MCF-7 human breast adenocarcinoma line and in the MCF-7Dox line, which was selected from MCF-7 by a resistance to multiple antitumor drugs (MDR). We have shown that acquisition of MDR was accompanied by a drastically reduced expression of some integrins of the beta1-subfamily (alpha2beta1, alpha3beta1, alpha6beta1) and of alpha vbeta5 intergin in the adenocarcinoma cells. In contrast, expression of alpha5beta1 integrin was markedly increased in the MDR cells. Along with multiple antitumor drug resistance, MCF-7Dox cells demonstrate elevated resistance to anchorage-dependent apoptosis (anoikis) and enhanced in vitro invasive activity. To elucidate the implication of beta1-integrins in the above phenotypic modifications, the effect of beta1-integrin signaling was assayed. Stimulation of beta1-mediated signaling was accomplished by treating of the cells with antibodies to the beta1-subunit common for members of the beta1-subfamily. These data show that activation of beta1-integrin signaling markedly upregulated anoikis of the adenocarcinoma cells.

Anoikis↗
PubMed2004

Expression and role of integrins in invasive activity of oncotransformed fibroblasts differing in spontaneous metastasizing.

Four closely related lines of RSV-transformed Syrian hamster fibroblasts differing drastically in their spontaneous metastatic capacity were investigated for the surface expression of integrins, in vitro invasion, and production of MMP-2 collagenase. The highly metastasizing HET-SR-2SC-LNM cells differ from the lowly metastasizing parental HET-SR cells in a high level of the surface expression of the collagen-specific alpha1beta1, alpha2beta1, and alphavbeta3 integrins, a high invasive activity, and an increased production of MMP-2. The same properties are characteristic for the actively metastasizing cells of the independent HET-SR-1 line. The lowly metastasizing fibroblasts that are derived from HET-SR-2SC-LNM retain a high level of the expression of the alpha1beta1 and alpha2beta1 integrins, but, unlike the parental line, they exhibit a decreased expression of the alphavbeta3 integrin, invasion in Matrigel, and MMP-2 production. Substrate stimulation of the signal function of the collagen-specific integrins increases the production of MMP-2 by the metastatically active fibroblasts. Inhibition of the signal activity of the integrins by RGD-containing pentapeptide or by genistein reduces markedly in vitro invasion in Matrigel and MMP-2 production. The role of specific properties of the extracellular matrix surrounding tumor cells and of specific surface integrins expressed in these cells in developing of the malignant phenotype is discussed.

Animals↗
PubMed2003

Role of integrin alphavbeta3 in substrate-dependent apoptosis of human intestinal carcinoma cells.

Incubation of human intestinal carcinoma Caco-2 cells in suspension (i.e., in the absence of substrate contacts) leads to massive cell death by apoptosis. Since this type of apoptosis has been referred to as anoikis, we designated these cells as anoikis-positive. However, a minor proportion of Caco-2 cells, designated as anoikis-negative, survived in suspension. Extended incubation of the cells in suspension resulted in the reduction of the number of viable cells. In comparison to the original Caco-2 cell population, the anoikis-negative cells demonstrated markedly decreased levels of expression of integrin alphavbeta3 on the cell surface and of transcription of the alphav subunit gene. Activation of the signaling function of alphavbeta3 in the original Caco-2 cells led to substantial stimulation of anoikis, while the inhibition of expression of this receptor resulted in better resistance of the cells to anoikis. The data provide the first evidence that alphavbeta3 integrin can generate apoptosis-stimulating signals.

Anoikis↗
PubMed2003

Integrins: structure and signaling.

Integrins are cell surface transmembrane glycoproteins that function as adhesion receptors in cell-extracellular matrix interactions and link the matrix proteins to the cytoskeleton. The family of human integrins comprises 24 members, each of which is a heterodimer consisting of 1 of 18 alpha- and 1 of 8 beta-subunits. Integrins play an important role in the cytoskeleton organization and in transduction of intracellular signals, regulating various processes such as proliferation, differentiation, apoptosis, and cell migration. This review summarizes current views on the structure of integrins, integrin associated proteins, and biochemical mechanisms underlying their signaling functions.

Animals↗
PubMed2001

Integrin alphavbeta3 promotes anchorage-dependent apoptosis in human intestinal carcinoma cells.

A population of cells surviving during prolonged incubation in suspension (anoikis-negative cells) were selected from the original anoikis-positive human intestinal carcinoma cell line Caco-2. Anoikis-negative cells are characterized by a strong transcriptional downregulation of the alphav-integrin chain as detected by FACS analysis, RT-PCR and Northern blotting. This finding suggested that alphav-integrin generates a signal stimulating apoptosis of Caco-2 cells upon their detachment from the extracellular matrix. Two lines of evidence supporting this suggestion were provided. First, activation of the alphavbeta3 integrin on Caco-2 cells by their treatment with an alphavbeta3-specific monoclonal antibody resulted in marked stimulation of anoikis. Second, treatment of Caco-2 cells with alphav-specific antisense oligonucleotide resulted in downregulation of the expression of alphav chain and in elevated resistance of these cells to anoikis. Thus, for the first time, our data prove that alphavbeta3 integrin can be an active transducer of apoptosis-stimulating signals generated in response to disruption of the cell-matrix contacts.

Anoikis↗
PubMed2000

Integrins: structure and functions.

Integrins are cell surface transmembrane glycoproteins which perform receptor functions in cell interactions with the extracellular matrix and cell-cell contacts. Another function of integrins is transduction of signals which mediate the effects of the matrix on the physiological activity of cells (motility, proliferation, differentiation, etc.). Contemporary views on the molecular structure of integrins and their involvement in the organization of the cytoskeleton and control of gene activity are presented. Biochemical mechanisms, by which the signal functions of integrins are realized, are discussed. The data on the participation of integrins in oncogenic cell transformation, metastasis, and apoptosis are analyzed.

Animals↗
PubMed1997

Integrin expression and collagenase activity of RSV-transformed Syrian hamster fibroblasts, differing in spontaneous metastasizing.

The expression of extracellular matrix (ECM) specific receptors, integrins, and the activities of type IV collagenase and interstitial collagenase were investigated in two strains of oncogenically transformed fibroblasts, drastically differing in spontaneous metastasizing. Both strains were shown to express quite limited patterns of integrins. Of those, alpha 5 beta 1 integrin is greatly reduced on highly metastatic (HM) cells, while the expression of alpha v beta 3 is strongly suppressed on lowly metastatic (LM) fibroblasts. No differences between the strains were found in either intracellular or secreted activities of type IV collagenase, while the activity of interstittial collagenase, secreted by HM cells, was twice as much as secreted by LM cells. The results imply the role of cooperated modifications of integrin-directed cell-ECM interaction and collagenase activity in establishing a metastatic phenotype.

Animals↗
PubMed1996

Beta 1 integrin subunit dimerization via disulfide bonds.

Integrins of the beta 1 family were isolated from human smooth muscle. SDS-PAGE analysis and subsequent immunoblotting demonstrated that integrin samples contain a protein immunologically related to beta 1 integrin subunit with the previously undescribed apparent molecular mass 205 kD. One-dimensional peptide mapping showed that the 205 kD protein is not a novel beta 1 related integrin subunit, but a beta 1 integrin subunit dimer. After reduction the major part of the beta 1 immunoreactive material migrated from the 205 kD to 130 kD region, indicating that beta 1 integrin subunit dimers were formed via disulfide bonds. When electrophoretically pure beta 1 monomer and dimer forms were analized it was found that during SDS-PAGE about 30% of beta 1 integrin subunit monomers were organized into dimers while approximately 70% of the beta 1 dimer form was partly disrupted into monomers. It was suggested that this steady-state process is a result of a reversible reaction between intra- and intermolecular disulfide bonds. Possible in vivo dimerization of integrins via disulfide bonds is discussed.

Chromatography, Affinity↗
PubMedDate not supplied

[The role of alphavbeta3 integrin in changes of the invasive phenotype in CP-transformed fibroblasts with multiple drug resistance].

A line of Syrian hamster RSV-ransformed fibroblasts having resistance to a number of cytostatics was shown to differ from the parental drug-sensitive line by an extremaly low expression of the integrin alpha v beta 3. In vitro invasive activity of the drug-resistrant cells appeared to be lower than that of their drug-sensitive counterparts. The role of integrin alpha v beta 3 in malignant phenotype and multiple drug resistance of tumor cells is discussed.

Animals↗
PubMedDate not supplied

[Electrophoretic characteristics of integrin++ beta1 subunit from human smooth muscles].

Total fraction of beta 1 integrin family was isolated from human smooth muscle by affinity chromatography on immobilized anti-beta 1 monoclonal antibodies. SDS-PAGE analysis and subsequent immunoblotting demonstrated that integrin samples contain unknown before high molecular mass (205 kD-nonreduced and 230 kD-reduced) material immunologically related to beta 1 integrin subunit. One dimensional peptide mapping showed that the 205 kD protein is not a novel beta 1 related integrin subunit, but a beta 1 integrin subunit dimer. Reduction of electrophoretic samples with dithiothreitol led to the removal of the major part of the beta 1 immunoreactive material from 205 kD to 130 kD region, indicating a disulfide nature of B1 integrin subunit dimer. The 230 kD protein turned out to be an only partly reduced beta 1 integrin disulfide bonded dimer. Possible in vivo existence of the disulfide bonded dimer and oligomer integrin forms is discussed.

Electrophoresis, Polyacrylamide Gel↗
PubMedDate not supplied

[Expression of integrins in human intestinal carcinoma cells differing in substrate specificity of apoptosis].

A cell population, characterized by a capacity to survive in the absence of cell attachment to a substrate (anoikis-independent cells), was selected from the original anoikis-dependent human gut carcinoma line Caco-2. In cell-adhesion assays, anoikis-independent cells demonstrated much lower affinity to fibronectin compared to their anoikis-dependent counterparts. No differences were found between the cell types in their surface expression of integrins alpha 1 beta 1, alpha 2 beta 1, alpha 3 beta 1, alpha 5 beta 1, and alpha 6 beta 1, while integrins alpha v beta 1 and alpha v beta 3 appeared to be much more actively expressed by the anoikis-dependent population. The procedure we have proposed for obtaining of cell populations having closely similar origination, while differing in anchorage-dependent apoptosis, provides a suitable model for investigation of apoptotis and the role of integrins in its mechanism.

Apoptosis↗