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Biomedical subjects

G E Morozevich

Publications and source records attributed to G E Morozevich.

15 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↗
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↗
PubMed1990

Secretion and intracellular degradation of collagen in cultures of normal and SV-40-transformed human fibroblasts.

With a pulse-chase technique, secretion and intracellular degradation of collagen were investigated in human cultured normal and SV-40-transformed fibroblasts. Normal cells at a proliferative phase of growth secreted collagen more actively than the stationary phase (resting) cells. Transformed fibroblasts secreted protein at a lower rate than both normal cell types. Resting and dividing normal cells displayed no differences in the rates of intracellular collagen degradation at the various stages of the chase period. Transformed cells did not differ from the normal ones in collagen degradation rates at the first hour of the chase period while at later times in the chase period, the total amount of degraded collagen was reduced by 20-30% in the transformed vs normal cultures. The data are discussed in the view of possible relations between the various mechanisms of intracellular transport and degradation of collagen.

Cell Division↗
PubMed1987

[Biosynthesis and secretion of collagen in normal and SV-40 virus-transformed human embryonal fibroblasts].

The biosynthesis and secretion of collagen proteins was studied in cultures of normal human embryo fibroblasts at different passages and growth stages as well as in cultures of human embryo fibroblasts transformed by oncogenic virus SV-40. It was found that normal fibroblasts maintain at a constant level the collagen synthesis throughout 20 passages, which is typical of proliferating and resting cells. Virus-transformed cells produce 3-4 times less collagen proteins on a per cell count. Normal and transformed fibroblasts do not differ in terms of total protein synthesis. Secretion of collagen and non-collagen proteins in transformed cell cultures appeared to be much lower than in normal cell cultures. Study of synthesized proteins by polyacrylamide gel electrophoresis showed that both types of cells secrete collagen proteins predominantly as polymers containing interchain S-S bonds of 3-helix molecules. Study of the protein-synthesizing activity of two polysomal fractions, i.e. membrane bound and free polysomes, isolated from the cells of both types in a cell-free system showed that membrane-bound polysomes from transformed fibroblasts synthesize collagen much less actively in comparison with normal cells. However, in transformed cells free polysomes, in contrast with normal cells, are active participants of a cell-free collagen protein synthesis.

Cell Line↗
PubMedDate not supplied

[Delta5-7-Ketosterols with modified side chain: the synthesis and the effects on viability and cholesterol biosynthesis in Hep G2 cells].

(22E)-3beta-Hydroxysitosta-5,22-dien-7-one, (22R, 23R)-3beta,22,23-trihydroxysitost-5-en-7-one, and (22R, 23R)-3beta-hydroxy-22,23-isopropylidenedioxysitost-5-en-7-one were synthesized. The cytotoxicity and effects on cholesterol biosynthesis of the resulting 7-ketosterols, 7-ketocholesterol, and (22S,23S)-3beta-hydroxy-22,23-oxidositost-5-en-7-one were studied in hepatoblastoma Hep G2 cells.

Cell Line, Tumor↗
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

[Determination of procollagen type III aminopropeptide by a solid phase method using antibodies conjugated with peroxidase or protein A labelled with radioactive iodine].

A solid-phase assay was developed for estimation of procollagen III aminopropeptide which involved both immunoenzymatic and radioimmune procedures. The assay did not require the iodine-labelled aminopropeptide, while content of the antigen was estimated using the conjugate of secondary antibodies and peroxidase or iodine-labelled protein A. Substitution of the protein A for the antibodies conjugate and peroxidase enabled to abolish the radioactive materials use.

Animals↗
PubMedDate not supplied

[Characteristics of collagen preparations labelled in vitro by 14C-acetic anhydrides. Their use for the determination of collagenase activity and as radioactive markers].

A modified procedure in developed for acetylation by means of 14C-acetic anhydride of highly purified collagen I preparations. The acetylated collagen exhibited high specific radioactivity and was effectively hydrolyzed by bacterial collagenase. The 14C-acetylated collagen was used as a radioactive marker in electrophoretic analysis of labelled proteins.

Acetates↗