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PubMed1998

Density-dependent regulation of cell-surface association of matrix metalloproteinase-2 (MMP-2) in breast-carcinoma cells.

Degradation of extracellular matrix takes place in areas of cell-matrix contacts and is partly carried out by the action of matrix metalloproteinases (MMP). MMP-2 is a member of the MMP family that has been associated with breast-cancer metastasis. In the present study, we investigated the association of MMP-2 to the surface of breast-cancer cells and revealed an MMP-2-binding site that is expressed on sparsely plated cells and which is progressively lost as the cells approach confluence. Gelatin zymography, immunostaining and flow cytometry of MDA-MB-231 cells from sparse cultures demonstrated binding both of latent and of activated exogenous MMP-2, while little or no binding of MMP-2 was observed in confluent culture. Analysis of the expression of MTI-MMP, TIMP-2 and alpha(v) integrin, 3 proteins shown to play a role in cell-surface association of MMP-2, revealed enhanced levels of these proteins in confluent MDA-MB-231 cells. Thus, the reduced MMP-2 binding to confluent cells is not related to a deficiency in these MMP-2-binding proteins. Taken together, these studies suggest that MMP-2 binding to the surface of breast-cancer cells is regulated by cell-cell interactions and that tumor cells invading from the main tumor mass can up-regulate their MMP-2-binding capacity to acquire greater invasive capacity.

Antigens, CD↗
PubMed1997

Neuronal differentiation in SH-SY5Y human neuroblastoma cells induces synthesis and secretion of tenascin and upregulation of alpha(v) integrin receptors.

Human SH-SY5Y neuroblastoma cells were induced to neuronal differentiation by using 12-0-tetradecanoylphorbol-13-acetate (TPA) and retinoic acid (RA). Both treatments rapidly induced long neurites and increased the content of neurofilaments as shown by immunocytochemistry and immunoblotting. Immunoprecipitation and immunoblotting of the culture medium with monoclonal antibodies demonstrated a rapid onset of synthesis and secretion of Mr 280,000 tenascin (Tn) polypeptide with TPA and both Mr 280,000 and 190,000 Tn polypeptides with RA and an increased secretion of extradomain A cellular fibronectin (EDA-Fn) upon both treatments. Upon RA treatment both Tn polypeptides were also found in extracellular matrix preparations of the differentiated cells. A diffuse extracellular Tn immunoreactivity and a distinct cytoplasmic reaction were seen in differentiated cells especially after exposure to monensin to inhibit cellular secretion. Instead, immunoprecipitation experiments suggested that laminin was synthesized by the cells but was not upregulated upon differentiation. Experiments with purified Tn, used to coat the culture substratum, demonstrated that the undifferentiated cells were unable to adhere or spread on Tn but rapidly acquired the spreading capacity upon differentiation with the inducing agents. In immunofluorescence and immunoblotting the undifferentiated cells presented only a faint heterogenous reaction for beta1 integrin (Int) subunit, whereas cells exposed to RA presented a strong reaction for the Int alpha1 and beta1 subunits, hence suggestive of Int alpha1beta1, and for Int alpha(v) subunit. Cells exposed to TPA showed an enhanced immunoreaction for Int alpha2 and beta1 subunits, suggestive of Int alpha2beta1, and for Int alpha(v) subunit. Immunoreactivity for Int alpha(v) located to distinct punctate plaques in the differentiated cells after both inducing agents. The results suggest that Tn is produced by cultured neuronally differentiating cells, and it is accompanied by the acquitance of an adhesion receptor for Tn.

Antigens, CD↗
PubMed1996

Non-RGD domains of osteopontin promote cell adhesion without involving alpha v integrins.

Osteopontin (OPN) is an integrin-binding secreted protein that contains an Arg-Gly-Asp (RGD) amino acid sequence and binds to various cell types via RGD-mediated interaction with the alpha v beta 3 integrin. We have identified a cell line whose binding to OPN does not require RGD or alpha v interactions. We compared the ability of two murine cell lines, L929 fibroblastic cells and B16-BL6 melanoma cells, to interact with OPN (from human milk, and recombinant human and mouse OPN) as well as recombinant OPN prepared to include either the N-terminal or C-terminal halves but lacking the RGD sequence. Both cell lines adhered to GRGDS peptides coupled to BSA, and these interactions were inhibited by addition of GRGDS (but not GRGES) peptides or a monoclonal antibody specific to the alpha v integrin subunit. Adhesion of L929 cells to OPN was also dependent on the RGD sequence and the alpha v integrin subunit. However, the binding of B16-BL6 cells was not inhibited by either GRGDS peptides or the anti-alpha v antibody. B16-BL6 (but not L929) cells were also able to adhere to and spread on both N-terminal and C-terminal OPN proteins that lack the RGD sequence, and these interactions were not inhibited by either GRGDS peptides or anti-alpha v antibody. Together these results indicate that B16-BL6 cells can adhere to OPN by interactions that are independent of either the RGD sequence or the alpha v integrin subunit, and suggest that some cells can interact with additional, non-RGD binding sites in OPN.

Amino Acid Sequence↗
PubMedDate not supplied

Efficient adenoviral gene transfer to kidney cortical vasculature utilizing a fiber modified vector.

BACKGROUND: The alpha v integrin is present in vascular endothelium, including that of the kidney. It is also upregulated in the presence of inflammatory cytokines and in some neoplasms. In an effort to transduce vascular endothelial cells, we compare in vitro and in vivo adenoviral gene transfer of a vector with a high affinity peptide ligand to the alpha v integrin incorporated into the fiber coat protein AdZ.F(RGD) to an unmodified vector, AdZ. METHODS: Cell transduction assays were performed on human umbilical vein endothelial cells (HuVEC) and human pulmonary epithelial cells (A549). In vitro competition assays were performed in the presence of either wild type (F5K) or chimeric (F5K(RGD)) soluble recombinant fiber protein. Transduction efficiency was determined by quantitative beta-galactosidase activity. In vivo gene transfer was compared infusing either AdZ or AdZ.F(RGD) into the left renal artery of the rat and assaying beta-galactosidase staining of the kidney. Gene transfer was also evaluated in the presence of a competitive RGD or control RGE peptide. RESULTS: There was a marked increase in transgene expression in HuVEC cells with AdZ.F(RGD) as compared to AdZ. The increased expression with AdZ.F(RGD) was more prominent in the endothelial as opposed to the epithelial cell line. Furthermore pre-incubation of these cells with either F5K or F5K(RGD) soluble fiber protein markedly decreased beta-galactosidase activity of AdZ, whereas only the F5K(RGD) decreased beta-galactosidase activity of AdZ.F(RGD). AdZ.F(RGD) also resulted in significantly enhanced beta-galactosidase expression in the vascular endothelium of the kidney (for comparable amounts of virus injected) as well as significantly higher gene transfer to cortical vasculature. Coinfusion of an RGD peptide with AdZ.F(RGD) blocked gene transfer whereas a control RGD peptide did not. CONCLUSION: We conclude that incorporating a high affinity peptide ligand into the adenoviral fiber protein can preferentially enhance in vitro and in vivo adenoviral transfection efficiency in endothelial cells. Enhancing transfection efficiency will not only broaden the scope of disease processes addressed with adenoviral vectors but also allow the use of lower titer, thereby limiting toxicity. This vector has additional potential to transduce endothelial cells within tumors or ischemic tissue where alpha v integrins are upregulated.

Adenoviridae↗
PubMed2006

Antiangiogenic combination tumor therapy blocking alpha(v)-integrins and VEGF-receptor-2 increases therapeutic effects in vivo.

Anti-angiogenesis is a promising strategy for cancer therapy currently evaluated in clinical trials. The aim of the study was to investigate the effects of an antiangiogenic combination therapy inhibiting alpha(v)-integrins by a c(yclic)RGD-peptide (EMD270179) and blocking VEGFR-2 by SU5416 on tumor angiogenesis and progression in vivo. Experiments were performed in dorsal skinfold chamber preparations of Syrian golden hamsters (60 +/- 5 g) bearing A-Mel-3 tumors. From day 3-10 after tumor-cell implantation, animals (n = 6 per group) were treated by monotherapies using the cRGD-peptide (114 mg/kg/day; i.p.), the VEGFR-2 antagonist (6 mg/kg/day; i.p.) or by the combination of both monotherapies. A control group received only the solvent DMSO. Using intravital microscopy parameters of intratumoral microcirculation were analyzed on day 5, 7 and 10. In separate experiments subcutaneous tumor growth and metastasis formation was evaluated starting therapy on day 0. Functional vessel density was significantly reduced by the combination therapy compared to that by all other groups on day 10. Although intratumoral red blood cell velocity and vessel diameters were less affected, blood flow in vessel segments and the microcirculatory perfusion index were lower after combined therapy compared to controls. In addition, we observed a significantly stronger inhibition of subcutaneous tumor growth and metastasis formation using the combination therapy. These data clearly support the concept of antiangiogenic combination therapy and demonstrate that it may especially be effective when scheduled as an early or prophylactic treatment regimen, thus avoiding angiogenesis-dependent tumor and metastasis initiation or tumor recurrence.

Angiogenesis Inhibitors↗
PubMed2003

Modulation of bone ingrowth and tissue differentiation by local infusion of interleukin-10 in the presence of ultra-high molecular weight polyethylene (UHMWPE) wear particles.

Interleukin-10 (IL-10) is a cytokine that plays a major role in suppressing the inflammatory response, particularly cell-mediated immunity that is characteristic of the TH1 response. The purpose of this study was to determine whether local infusion of IL-10 could mitigate the suppression of bone ingrowth associated with polyethylene wear particles. Drug test chambers were implanted in the proximal tibia of 20 mature New Zealand White rabbits. The DTC provided a continuous 1 x 1 x 5-mm canal for tissue ingrowth. After a 6-week period for osseointegration, the DTC was then connected to an osmotic diffusion pump. IL-10 at doses of 0.1-100 ng/mL (0.25 microL/h) was infused with or without ultra-high molecular weight polyethylene particles (0.5 +/- 0.2 microm diameter, 10(12) particles/mL) present in the chamber for a 3- or 6-week period. The tissue in the chamber was harvested after each treatment; sections were stained with hematoxylin and eosin for morphometric analysis. Osteoclast-like cells were identified by immunohistochemical staining using a monoclonal antibody directed against the alpha chain of the vitronectin receptor, CD51. Osteoblasts were identified using alkaline phosphatase staining. In dose-response studies, infusion of 1 ng/mL IL-10 yielded the greatest bone ingrowth in the presence of particles. The addition of polyethylene particles evoked a marked foreign body reaction and fibrosis; bone ingrowth was significantly suppressed (p = 0.0003). Bone ingrowth was increased by over 48% with infusion of IL-10 for the final 3 weeks of a 6-week ultra-high molecular weight polyethylene particle exposure compared with particles alone (p = 0.027). IL-10 is a cytokine that plays a major role in suppressing the inflammatory response, especially cell-mediated immunity that is characteristic of the TH1 response. Local infusion of immune-modulating cytokines such as IL-10 may prove to be useful in abating particle-induced periprosthetic osteolysis.

Alkaline Phosphatase↗
PubMed2007

Integrin alpha(5) controls osteoblastic proliferation and differentiation responses to titanium substrates presenting different roughness characteristics in a roughness independent manner.

Integrin alpha(5)beta(1) regulates osteoblast proliferation and differentiation on smooth synthetic surfaces presenting different chemistries, but it is not known whether this integrin controls osteoblast behavior on surfaces that have micron-scale rough topographies. We cultured MG63 human osteoblast-like cells on titanium substrates with three different roughness characteristics: chemically polished (PT), grit blasted and acid etched with a complex topography consisting of 20-100 mum craters and 0.5-2 mum micropits (SLA), and plasma-sprayed Ti with irregular projections (TPS). Cells spread well on PT but displayed a smaller footprint on SLA or TPS. Nuclei were larger on PT as well. alpha(5)beta(1) binding and FAK phosphorylation were greater on the rougher surfaces (TPS > SLA > PT). Antibodies against the alpha(5)beta(1) binding site on fibronectin had no effect on cell number at 3 days, but [(3)H]-thymidine incorporation was increased, suggesting that binding to fibronectin was necessary for cell cycle regulation. Antibodies to the alpha(5) subunit reduced cell number at 3 days on PT and TPS and reduced DNA synthesis on all substrates in a surface microstructure-independent manner. At 7 days, cell numbers were reduced on PT, and DNA synthesis was reduced by 50% on all surfaces. At 7 days, anti-alpha(5) antibodies caused a partial reduction in alkaline phosphatase enzyme activity on all surfaces, but this effect was independent of surface microstructure. These results indicate that surface micron-scale topography modulates alpha(5)beta(1) integrin binding and FAK activation. Signaling via alpha(5)-dependent mechanisms is required for DNA synthesis and regulation of alkaline phosphatase, but this effect is independent of surface microstructure.

Alkaline Phosphatase↗
PubMed2001

Plasminogen activator inhibitor-1 regulates cell adhesion by binding to the somatomedin B domain of vitronectin.

Plasminogen activator inhibitor-1 (PAI-1) binds to the somatomedin B (SMB) domain of vitronectin. It inhibits the adhesion of U937 cells to vitronectin by competing with the urokinase receptor (uPAR; CD87) on these cells for binding to the same domain. Although the inhibitor also blocks integrin-mediated cell adhesion, the molecular basis of this effect is unclear. In this study, the effect of the inhibitor on the adhesion of a variety of cells (e.g., U937, MCF7, HT-1080, and HeLa) to vitronectin was assessed, and the importance of the SMB domain in these interactions was determined. Although PAI-1 blocked the adhesion of all of these cells to vitronectin-coated wells, it did not block adhesion to a variant of vitronectin which lacked the SMB domain. Interestingly, HT-1080 and U937 cells attached avidly to microtiter wells coated with purified recombinant SMB (which does not contain the RGD sequence), and this adhesion was again blocked by the inhibitor. These results affirm that PAI-1 can inhibit both uPAR- and integrin-mediated cell adhesion, and demonstrate that the SMB domain of vitronectin is required for these effects. They also show that multiple cell types can employ uPAR as an adhesion receptor. The use of purified recombinant SMB should help to further define this novel adhesive pathway, and to delineate its relationship with integrin-mediated adhesive events.

Antigens, CD↗
PubMed2007

P2Y2 receptors induced cell surface redistribution of alpha(v) integrin is required for activation of ERK 1/2 in U937 cells.

Nucleotides released from cells due to stress, injury or inflammation, induce mitogenic effects in monocytes via activation of P2Y(2) nucleotide receptors (P2Y(2)Rs). Here we show that P2Y(2) nucleotide receptors in U937 monocytic cells regulate the activation of extracellular signal-regulated kinases 1 and 2 (ERK 1/2) by inducing the clustering of alpha(v) integrins. The activation of phosphatidylinositol 3-kinase by P2Y(2)R ligands was required for alpha(v) clustering, suggesting a means whereby two different classes of receptors communicate to induce mitogenic responses in monocytic cells. P2Y(2)R-induced alpha(v) clustering was also associated with a flattened phenotype of the U937 cells, consistent with the role of the P2Y(2)R in regulating early events in cell migration.

Calcium↗
PubMed2004

Development of an adenoviral vector system with adenovirus serotype 35 tropism; efficient transient gene transfer into primary malignant hematopoietic cells.

BACKGROUND: A paucity of coxsackie adenovirus receptor (CAR) hampers the adenovirus serotype 5 (Ad5)-based vector-mediated gene transfer into malignant hematopoietic cells. Fiber-retargeted adenoviral vectors with species B tropism can potentially bypass the CAR requirement and facilitate efficient gene transfer into malignant hematopoietic cells. METHODS: For feasible generation of fiber-retargeted adenoviral vectors, we have modified the versatile AdEasy system with a chimeric fiber gene encoding the Ad5 fiber tail domain and Ad35 fiber shaft and knob domains. An Ad5-based vector encoding the green fluorescent protein (GFP) gene under the control of the PGK promoter with Ad35 fiber receptor specificity was generated (Ad5F35-GFP). The Ad5F35-GFP vector-mediated gene transfer efficiency was compared with a fiber non-modified Ad5-GFP vector, which also encodes the GFP gene under the control of the PGK promoter. RESULTS: We demonstrated that a variety of Ad5-refractory malignant myeloid and B lymphoid cell lines were highly permissive to the Ad5F35-GFP vector infection. Importantly, primary chronic myeloid leukemic (CML) cells and chronic lymphocytic leukemia (CLL) B cells were superiorly transduced by the Ad5F35-GFP vector at a multiplicity of infection (MOI) of 100 compared with the Ad5-GFP vector. CONCLUSIONS: Our study will facilitate the generation of fiber-retargeted adenoviral vectors and enable transient genetic manipulation of primary malignant hematopoietic cells.

Adenoviridae↗
PubMed1999

Up-regulation of integrin alpha5 by a C-terminus four-amino-acid sequence of substance P (phenylalanine-glycine-leucine-methionine- amide) synergistically with insulin-like growth factor-1 in SV-40 transformed human corneal epithelial cells.

We previously reported that substance P and insulin-like growth factor-1 (IGF-1) synergistically facilitate corneal epithelial migration in vivo and in vitro. We investigated whether the substance P-derived tetrapeptide (phenylalanine-glycine-leucine-methionine-amide, FGLM) can up-regulate the receptors for fibronectin and cellular adhesion to fibronectin matrix in the presence or absence of IGF-1 in cultured SV-40 transformed human corneal epithelial (HCE) cells. The combination of both FGLM and IGF-1 and substance P and IGF-1 significantly increased the number of cells adhered to the fibronectin matrix and the expression of integrin alpha5. The synergistic effect of FGLM and IGF-1 on the adhesion of HCE cells to the fibronectin matrix is partly carried through up-regulation of integrin alpha5 expression in HCE cells. These results showed that the four-amino-acid sequence at the C-terminus of substance P completely mimics the substance P molecule in terms of synergism with IGF-1 on adhesion of epithelial cells to the fibronectin matrix.

Antigens, CD↗
PubMed2001

Downregulated expression of integrin alpha6 by transforming growth factor-beta(1) on lens epithelial cells in vitro.

Integrins represent the main cell surface receptors that mediate cell-matrix and cell-cell interactions. They play critical roles in adhesion, migration, morphogenesis, and the differentiation of several cell types. Previous studies have demonstrated that members of the fibroblast growth factor (FGF)-2, transforming growth factor (TGF)-beta(1), and insulin growth factor (IGF)-1 play important roles in lens biology. In particularly, TGF-beta(1) appears to play a key role in extracellular matrix production, cell proliferation, and cell differentiation of lens epithelial cells. In this study we investigated the effects of FGF-2, TGF-beta(1), and IGF-1 on the modulation of integrin receptors using lens epithelial cell lines (HLE B-3 and alphaTN-4) and lens explants. We found that the expression of integrin alpha6 is downregulated by TGF-beta(1), but is not responsive to FGF-2 or IGF-1. The promoter activity of the integrin alpha6 gene decreased upon TGF-beta(1) treatment in a transient transfection assay, and flow cytometric analysis demonstrated the reduced expression of integrin alpha6 by TGF-beta(1), whereas significant changes were not observed in the level of integrin alpha6 after the addition of FGF-2. These findings suggest that the reduced expression of integrin alpha6 caused by TGF-beta(1) might play a role in the activation of the cell cycle genes required during the fiber differentiation of the lens.

Animals↗
PubMed1995

Differential short-term transduction efficiency of adult versus newborn mouse tissues by adenoviral recombinants.

We demonstrated different transduction efficiency in several major organs of the immature (newborn) versus mature (adult) mice using adenoviral recombinants containing expression cassettes for either firefly luciferase or bacterial beta-galactosidase reporter genes. The studied tissues included skeletal muscle, heart, brain, lung, kidney, and liver. The transduction efficiency in all tissues, especially skeletal muscle, was significantly less in adults than in newborns, with two exceptions. In the heart, transduction efficiency was the same in newborns and adults, while in brain, it was greater in the adult than in the newborn. The cited differences in transduction efficiencies between newborn and adult tissues applied approximately equally to both reporter genes. The alpha v integrin level showed the same trend as the transduction efficiency in all tissues, except the heart. Polymerase chain reaction showed a specific adenoviral product in proportion to the reporter gene expression in muscle, heart, and brain. The results of this study should be considered in designing gene therapy strategies in genetic diseases.

Adenoviridae↗
PubMed2002

Gonadotropin stimulation of MLS human epithelial ovarian carcinoma cells augments cell adhesion mediated by CD44 and by alpha(v)-integrin.

OBJECTIVE: The goal of this work was to evaluate the involvement of gonadotropins in the regulation of adhesion of human epithelial ovarian carcinoma. We studied two pathways that were previously implicated in the metastatic implantation of ovarian carcinoma to the peritoneum, namely hyaluronan-CD44 and RGD-integrin mediated adhesion. METHODS: Two cell lines derived from human epithelial ovarian carcinoma (MLS and OC238) were stimulated with luteinizing hormone (LH) and/or follicle stimulating hormone (FSH). Expression of CD44 was evaluated by Western blotting. Expression of alpha(v)-integrins was studied by RT-PCR and Northern blot. Integrin and CD44 mediated adhesion of the cells was analyzed using culture plates coated either with a thrombin derived RGD containing peptide or fibronectin for integrin mediated adhesion or with hyaluronan for CD44 mediated adhesion. RESULTS: MLS cells stimulated with either LH or FSH showed increased adhesion to culture plates coated with hyaluronan, as well as to culture plates coated with fibronectin or with a thrombin derived RGD containing peptide. In these cells, gonadotropin stimulation led to induced expression of the integrin subunit alpha(v) and CD44, the cell surface hyaluronan receptor. On the other hand, OC238 cells showed no expression of the integrin subunit alpha(v) and no hormonal effect on the expression of CD44. Accordingly, adhesion of OC238 cells on either RGD or CD44 was not affected by hormonal stimulation. CONCLUSION: Elevated levels of gonadotropins may in some cases facilitate peritoneal metastatic dissemination of ovarian cancer by increasing cell adhesion, the first essential step in the invasion process.

Antigens, CD↗
PubMed1998

Integrin alpha v promoter activity in keratinocytes.

BACKGROUND: During reepithelialization keratinocytes show increased expression of the integrin subunit alpha-v. We have investigated the promoter region of the alpha-v integrin subunit to learn more about its regulation. METHODS: The promoter region of the human integrin alpha-v gene was cloned into a luciferase reporter vector. Deletional mutants were created using PCR. Computerized sequence analysis was performed using the Wisconsin Package. Gel-shift analysis was performed using keratinocyte nuclear extracts and oligonucleotides spanning th regions of interest. RESULTS: Deletion from -522 bp to -235 resulted in no discernible effect on promoter activity. In contrast deletion of the next 22 bp, which included a putative ets binding site, reduced activity by approximately half. Further deletion to -139 bp essentially abolished promoter activity. Computer searching of this region of the integrin alpha-v promoter revealed two tandemly repeated motifs, TCCTCCTCC, that had previously been implicated in the function of the epidermal growth factor receptor (EGFR) promoter. Comparison of the alpha-v integrin promoter to the EGFR promoter revealed an area of high homology in this region. Gel-shift analysis revealed binding of a single-strand specific DNA binding protein to single stranded oligos comprising these motifs, but no binding of factors to the double- stranded oligo containing the ets binding site. CONCLUSIONS: In keratinocytes alpha-v integrin expression is controlled by a region of the promoter with high homology to the epidermal growth factor receptor promoter This region binds single-strand specific DNA binding proteins that are likely to be important in controlling transcription.

Antigens, CD↗
PubMed2001

Variation in adenovirus receptor expression and adenovirus vector-mediated transgene expression at defined stages of the cell cycle.

Detailed investigations have addressed the infection pathway of recombinant adenovirus (Ad) gene transfer vectors, but little attention has been paid to the influence of cell physiology on the outcome of Ad infection. Based on observations that Ad infection of clonal cell populations show cell-to-cell variability in the extent of capsid binding, we hypothesized that the cell cycle may influence the outcome of Ad infection. To address this hypothesis, we evaluated Ad association with cells in both unsynchronized and pharmacologically synchronized cell populations. In unsynchronized cell populations, elevated Ad association with cells correlated with expression of cyclin B1, a marker of entry into the M phase of mitosis. The same analysis conducted on cell populations that were synchronized at M phase (using paclitaxel or nocodazole) or at S phase (using aphidicolin) confirmed that M phase cells bound three- to sixfold more capsid compared with unsynchronized cells, which are primarily in the G(1) and G(2) phases. The elevated association of vectors with cells translated into 2.5- to 4-fold greater transgene expression 24 hours after infection. Assessment of cell surface expression of Ad receptors demonstrated that both the high-affinity coxsackie-adenovirus receptor for Ad fiber protein and the low-affinity alpha(v) integrin receptor for Ad penton base protein showed increased cell surface expression at M phase (1.5-fold and 2- to 3-fold increases, respectively). These data demonstrate that Ad infection of a homogenous population of cells can vary depending on the cell cycle stage, with enhanced Ad binding and expression correlating with the enhanced expression of Ad receptors during M phase. These observations have relevance to understanding the mechanisms of gene transfer by Ad vectors and should help in the design of in vivo gene transfer strategies.

Adenoviridae↗