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PubMed2004

Temporal dissection of beta1-integrin signaling indicates a role for p130Cas-Crk in filopodia formation.

Invasin-promoted spreading of beta1-integrin-deficient cells, transfected with the beta1A- or beta1B-integrin splice variants, were used to dissect early beta1-integrin signaling events. The beta1B isoform, which has a different membrane-distal part of the cytoplasmic tail from beta1A, is defective in signaling and function. When plated on surfaces coated with the high affinity ligand invasin, beta1B-integrin-expressing cells spread by forming filopodia with distinct adhesive phosphotyrosine complexes at the tips, without signs of lamellipodia. This suggested that the beta1B-integrin mediated a partial signaling sufficient for formation of filopodia but insufficient for lamellipodia formation. When screening for proteins present in the distal filopodial phosphotyrosine complexes of beta1B cells, p130Cas and the filopodia proteins vasodilator-stimulated phosphoprotein and talin were found, whereas the typical focal complex proteins focal adhesion kinase, paxillin, and vinculin were not. Invasin-promoted adhesion induced complex formation of p130Cas and the adapter Crk. Moreover, Crk together with Dock180 were present at the filopodial tips of beta1B-integrin-expressing cells, and there was a prominent Rac1 activation. Expression of dominant negative variants of p130Cas or CrkII blocked beta1B-integrin-mediated filopodia formation, indicating that this signaling scaffold is central in this process.

Animals↗
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↗
PubMed1997

Yersinia invasin, a bacterial beta1-integrin ligand, is a potent inducer of lymphocyte motility and migration to collagen type IV and fibronectin.

The Yersinia pseudotuberculosis invasin protein was found to be a potent inducer of pseudopodia formation and chemotactic and haptotactic migration in human T lymphocytes. Checkerboard analysis confirmed that migration was directional. The Yersinia invasin triggered migration of otherwise poorly migratory normal T cells on fibronectin and in particular on collagen type IV, and augmented the migration of leukemic T cell lines on these components. Invasin-induced lymphocyte migration was inhibited by staurosporin that selectively prevented pseudopodia formation but, noteworthy, augmented adhesion. The motogenic and attractant properties of invasin (Inv) were mediated via beta1-integrins, as shown by lack of effect of Inv on the motility of a beta1-integrin-negative lymphoid cell line and inhibition of invasin-induced lymphocyte motility by anti-beta1 Abs. Inv was markedly more effective than the extracellular matrix components fibronectin, collagen type IV, and laminin, which also interact with lymphocyte beta1-integrins, with respect to induction of pseudopodia, chemotaxis, and haptotaxis. Thus, Yersinia invasin is a model ligand for induction of lymphocyte motility via beta1-integrins. The extraordinary capacity of Inv to trigger and guide T lymphocyte motility and potentiate lymphocyte migration to extracellular matrix components may be of pathogenetic significance for the movement of lymphocytes to extraintestinal sites secondary to Yersinia infection.

Adhesins, Bacterial↗
PubMed2005

Beta1 integrins and neural stem cells: making sense of the extracellular environment.

Neural Stem Cells (NSC) are present in the developing and adult CNS. In both the embryonic and adult neurogenic regions, beta1 integrins may act as sensors for the changing extracellular matrix. Here we highlight the integrative functions that beta1 integrins may play in the "niche" by regulating NSC growth factor responsiveness in a timely and spatially controlled manner. beta1 integrins may provide NSC with the capacity to react to a dynamic "niche", and to respond adequately by either remaining as stem cells or by differentiating and migrating away to shape the developing cortex.

Animals↗
PubMed2000

Quantitative study of beta1-integrin expression and fibronectin interaction profile of T lymphocytes in vitro infected with HIV.

Cell-extracellular matrix interactions, regulated in part by beta1-integrins, play a key role in the recirculation of T lymphocytes and tissue infiltration in inflammatory and immune responses. HIV infection may affect CD4+ T cell adhesion, and the trafficking and migration of these cells, which are crucial for foreign antigen recognition. We investigated this by studying the expression of the beta1-integrin chains CD29 and CD49c, -d, -e, and -f, on in vitro HIV-infected primary T cells. We also assessed fibronectin binding and production by CD4+ lymphocytes. X4 (HIV-1/LAI), R5 (HIV-1/Ba-L), and X4R5 (HIV-2/ROD) strains, and X4R5 primary isolates (HIV-1/DAS, HIV-1/THI), with different cytopathogenicity and replication kinetics, were used. Beta1-integrin expression on CD4+ and CD4- T cell subpopulations was regulated by cell activation with phytohemagglutinin-P and interleukin 2, but was unaffected by HIV infection, even at the peak of viral replication and CD4+ cell depletion. Similarly, fibronectin binding to CD4+ lymphocytes was not affected by HIV infection. This suggests that infected lymphocytes may be able to extravasate, migrate, and recirculate within the body until their death.

Blood Donors↗
PubMed1998

Beta1 integrins participate in the hypertrophic response of rat ventricular myocytes.

Multiple signaling pathways have been implicated in the hypertrophic response of ventricular myocytes, yet the importance of cell-matrix interactions has not been extensively examined. Integrins are cell-surface molecules that link the extracellular matrix to the cellular cytoskeleton. They can function as cell signaling molecules and transducers of mechanical information in noncardiac cells. Given these properties and their abundance in cardiac cells, we evaluated the hypothesis that beta1 integrin function is involved in the alpha1-adrenergic mediated hypertrophic response of neonatal rat ventricular myocytes. The hypertrophic response of this model required interaction with extracellular matrix proteins. Specificity of these results was confirmed by demonstrating that ventricular myocytes plated onto an anti-beta1 integrin antibody supported the hypertrophic gene response. Adenovirus-mediated overexpression of beta1 integrin augmented the myocyte hypertrophic response when assessed by protein synthesis and atrial natriuretic factor production, a marker gene of hypertrophic induction. DNA synthesis was not altered by integrin overexpression. Transfection of cultured cardiac myocytes with either the ubiquitously expressed beta1A integrin or the cardiac/skeletal muscle-specific beta1 isoform (beta1D) activated reporter expression from both the atrial natriuretic factor and myosin light chain-2 ventricular promoters, genetic markers of ventricular cell hypertrophy. Finally, suppression of integrin signaling by overexpression of free beta1 integrin cytoplasmic domains inhibited the adrenergically mediated atrial natriuretic factor response. These findings show that integrin ligation and signaling are involved in the cardiac hypertrophic response pathway.

Adenoviridae↗
PubMed2000

Functional relevance of activated beta1 integrins in mercury-induced nephritis.

Cell adhesion through different adhesion molecules is a crucial event in the inflammatory response. Integrins can only bind and mediate cellular adhesion after their activation by different specific stimuli. The state of beta1 integrin activation can be assessed by a group of monoclonal antibodies (HUTS) that selectively recognize beta1 integrins in their active form. A similar activated epitope in the rat was defined using the anti-human monoclonal antibody HUTS-21, which recognizes an activation-dependent epitope on the beta1 chain. It was found that the divalent cations Mn(2+) and Hg(2+) were able to induce in vitro the activation of beta1 integrins on rat lymphocytes. The Hg(2+) cation induces an autoimmune disease in the Brown Norway rat characterized by synthesis and glomerular deposits of anti-glomerular basement membrane antibodies, proteinuria, and interstitial nephritis. Using the mercury model of nephritis, it was found that the expression of HUTS-21 epitope is induced in vivo in rat lymphocytes, and its appearance is correlated with the other parameters at the onset of the disease. In addition, the administration of HUTS-21 monoclonal antibody to HgCl(2)-treated rats offered evidence of its protective effects (1) against infiltration of renal interstitium by leukocytes, and (2) in the reduction of anti-glomerular basement membrane synthesis and glomerular deposition. Nevertheless, urinary protein values remained unaffected. These results demonstrate a key role of beta1-activated integrins in both leukocyte cell-cell interactions and leukocyte infiltration pathway mechanism, and also indicate that leukocyte migration may have less importance in the development of this disease than previously thought.

Analysis of Variance↗
PubMed2006

In vivo beta1 integrin function requires phosphorylation-independent regulation by cytoplasmic tyrosines.

Integrins are heterodimeric adhesion receptors associated with bidirectional signaling. In vitro studies support a role for the binding of evolutionarily conserved tyrosine motifs (NPxY) in the beta integrin cytoplasmic tail to phosphotyrosine-binding (PTB) domain-containing proteins, an interaction proposed to be dynamically regulated by tyrosine phosphorylation. Here we show that replacement of both beta1 integrin cytoplasmic tyrosines with alanines, resulting in the loss of all PTB domain interaction, causes complete loss of beta1 integrin function in vivo. In contrast, replacement of beta1 integrin cytoplasmic tyrosines with phenylalanines, a mutation that prevents tyrosine phosphorylation, conserves in vivo integrin function. These results have important implications for the molecular mechanism and regulation of integrin function.

Amino Acid Motifs↗
PubMed2002

Expression of focal adhesion kinase and alpha5 and beta1 integrins in carcinomas and its clinical significance.

AIM: To detect the expression pattern of FAK (focal adhesion kinase) and integrin alpha5 and beta1 subunits in different kinds of cancerous tissues and to study their correlation with clinicopathological data including tumor type, grade and lymph node status. METHODS: Using an immunohistochemical technique, we examined the expression of FAK and integrin and subunits in cancerous and noncancerous tissues obtained from 75 patients with gastric carcinomas, 21 colorectal carcinomas, 16 hepatocellular carcinomas, 20 uterocervical carcinomas, and 20 breast carcinomas. RESULTS: The staining of FAK was stronger in cancerous than in noncancerous areas. Enhanced expression of FAKwas detected in poor-differentiated carcinoma of the stomach and colorectum. Tumors with lymph node metastases had more FAK protein than those without metastases. In addition, the deeper the extent of tumor infiltration, the higher the FAK expression. The expression of integrin alpha5 and beta1 subunits was lower in cancerous areas than in noncancerous areas, but it was higher in well-differentiated cancerous tissues than in poor differentiated tissues. The relationship between the expression of integrin alpha5 and beta1 subunits and infiltration or metastasis was not significant. Cancerous tissues with stronger FAK expression (++ or +++) also had a higher expression of integrin alpha5 and beta1 subunits in the tumor and its unaffected margins. CONCLUSION: FAK is a better marker for carcinogenesis and the progression of cancer than integrin alpha5 and beta1 subunit, and it may be not only a transformation-linked enzyme but also a progression-linked enzyme.

Adult↗
PubMed2001

Immunoelectron microscopic localization of the neural recognition molecules L1, NCAM, and its isoform NCAM180, the NCAM-associated polysialic acid, beta1 integrin and the extracellular matrix molecule tenascin-R in synapses of the adult rat hippocampus.

We have investigated the possibility that morphologically different excitatory glutamatergic synapses of the "trisynaptic circuit" in the adult rodent hippocampus, which display different types of long-term potentiation (LTP), may express the immunoglobulin superfamily recognition molecules L1 and NCAM, the extracellular matrix molecule tenascin-R, and the extracellular matrix receptor constituent beta1 integrin in a differential manner. The neural cell adhesion molecules L1, NCAM (all three major isoforms), NCAM180 (the largest major isoform with the longest cytoplasmic domain), beta1 integrin, polysialic acid (PSA) associated with NCAM, and tenascin-R were localized by pre-embedding immunostaining procedures in the CA3/CA4 region (mossy fiber synapses) and in the dentate gyrus (spine synapses) of the adult rat hippocampus. Synaptic membranes of mossy fiber synapses where LTP is expressed presynaptically did not show detectable levels of immunoreactivity for any of the molecules/epitopes studied. L1, NCAM, and PSA, but not NCAM180 or beta1 integrin, were detectable on axonal membranes of fasciculating mossy fibers. In contrast to mossy fiber synapses, spine synapses in the outer third of the molecular layer of the dentate gyrus, which display postsynaptic expression mechanisms of LTP, were both immunopositive and immunonegative for NCAM, NCAM180, beta1 integrin, and PSA. Those spine synapses postsynaptically immunoreactive for NCAM or PSA also showed immunoreactivity on their presynaptic membranes. NCAM180 was not detectable presynaptically in spine synapses. L1 could not be found in spine synapses either pre- or postsynaptically. Also, the extracellular matrix molecule tenascin-R was not detectable in synaptic clefts of all synapses tested, but was amply present between fasciculating axons, axon-astrocyte contact areas, and astrocytic gap junctions. Differences in expression of the membrane-bound adhesion molecules at both types of synapses may reflect the different mechanisms for induction and/or maintenance of synaptic plasticity.

Animals↗
PubMed2006

Regulation of beta1 integrin expression in endothelial cells by chimeric tRNA(Val) ribozyme.

To downregulate expression of the beta1 integrin subunit in endothelial cells, plasmid encoding the ribozyme cassette containing hammerhead ribozyme flanked at the 5' terminus by tRNA(Val) and at the 3' terminus by constitutive transport element sequences was constructed. When used to transfect immortalized human endothelial cell line EA.hy 926, it selectively blocked the synthesis of the beta1 integrin subunit and thus inhibited migration and proliferation of the cells. Thus, this construct may be a valuable tool to control the proangiogenic phenotype of stimulated endothelial cells.

Cell Line↗
PubMed2006

Regulation of protein phosphatase 2A-mediated recruitment of IQGAP1 to beta1 integrin by EGF through activation of Ca2+/calmodulin-dependent protein kinase II.

Maintenance of beta1 integrin-mediated cell adhesion in quiescent human mammary epithelial (HME) cells requires protein phosphatase (PP) 2A for not only dephosphorylation of beta1 integrin but also recruitment of IQGAP1 to Rac-bound beta1 integrin. However, how PP2A-dependent regulatory machinery of cell adhesion responds to EGF remains to be elucidated. We report here that phosphorylated Ca2+/calmodulin-dependent protein kinase II (CaMKII) at threonine 286 was involved in the beta1 integrin complex that consisted of PP2A, Rac, and IQGAP1 in quiescent HME cells. Stimulation of the cells with EGF concomitantly induced an increase in intracellular Ca2+, activation of CaMKII, and dissociation of PP2A-IQGAP1-CaMKII from beta1 integrin-Rac. Because the activation of CaMKII and dissociation of PP2A-IQGAP1-CaMKII were blocked by either Ca2+-chelator or CaMKII inhibitor, we therefore propose that EGF has the ability to abrogate the PP2A function in the maintenance of beta1 integrin-mediated cell adhesion by dissociation of PP2A-IQGAP1-CaMKII from beta1 integrin-Rac through activation of CaMKII.

Calcium↗
PubMed2005

Involvement of beta1 integrin in microglial chemotaxis and proliferation on fibronectin: different regulations by ADP through PKA.

Microglia are immune cells in the brain; their activation, migration, and proliferation have pivotal roles in brain injuries and diseases. Microglia are known to attach firmly to fibronectin, the upregulation of which is associated with several pathological conditions in the CNS, through beta1 integrin and become activated. Extracellular nucleotides can serve as potent signaling molecules. Recently, ATP and ADP were revealed to possess chemoattractive properties to microglia via Gi-coupled P2Y receptors. In the present study, we report that the ADP-induced chemotaxis of microglia is mediated by P2Y12/13 receptors and is beta1 integrin-dependent in the presence of fibronectin. Signals from P2Y12/13 receptors also cause beta1 integrin translocation to the membrane ruffle regions, but this redistribution was lost when the intracellular cyclic AMP (cAMP) was increased by forskolin or dibutyryl cAMP. This inhibitory effect of cAMP-elevating agents did not appear when microglia were co-incubated with a protein kinase A (PKA) inhibitor, KT-5720, suggesting that PKA is a negative regulator of the beta1 integrin translocation. We also show that the engagement of beta1 integrin enhanced microglial proliferation. Signals from P2Y12/13 receptors attenuated the proliferation, whereas ADP itself had no effect on microglial growth. Furthermore, beta1 integrin-induced proliferation is positively regulated by the cAMP-dependent PKA. Together, these results indicate the involvement of beta1 integrin in microglial proliferation and chemotaxis, both of which have clinical importance. The data also suggest that PKA is inversely involved in these two cellular functions.

Adenosine Diphosphate↗
PubMed2004

[Integrin beta1 mediates hepatocellular carcinoma cells adhesion & chemotaxis to type IV collagen].

A micropipette technique was adopted to investigate the effect of blockade of integrin betal on adhesion of hepatocellular carcinoma (HCC) cells onto type IV collagen (Col IV) coated surfaces and pseudopod protrusion of HCC cells in response to Col IV stimulation. Adhesion strength was expressed as an adhesion force, which was defined as the product of the cross sectional area and critical negative pressure needed to detach single cell away from the substrate. Chemotactic pseudopod protrusion of an HCC cell was evaluated using a dual-pipette set-up, in which two pipettes filled with Col IV solution were positional in close contact with the same cell and pseudopod protrusion into each pipette was viewed dynamically and recorded with a tape recorder. The lengths of pseudopods were measured and plotted against time to obtain a pseudopod growth curve. The integrin beta1 subunit on the surfaces of HCC cells was analyzed by flow cytometry. The results showed that the adhesion forces for HCC cells adhering on 5 microg/ml Col IV coated surfaces were 932 +/- 134 (x 10(-10) N, n = 60). Upon treatment of HCC cells with Anti-CD29 in a protein concentration of 5 microg/ml and 10 microg/ml, the value decreased significantly to 449 +/- 119 (x 10(-10) N, n = 60) and 220 +/- 78 (x 10(-10) N, n = 55), respectively. In dual pipette chemotaxis experiment, when the two pipettes were filled with Col IV in an identical concentration of 600 microg/ml, pseudopods extended from the HCC cell into each of the pipettes nearly symmetrically, i.e., with nearly identical maximum pseudopod length and similar pseudopod growth curves. Upon addition of Anti-CD29 to one of the pipettes in a protein concentration of 20 microg/ml, pseudopod protrusion was blocked nearly completely while protrusion into the opposite pipette became more evidently, with larger maximum length. Expression of integrin beta1 was up to 95.78% to cells chosen in the experiment. These results suggested that integrin beta1 subunit was important constituent receptor subunit for mediating HCC cell adhesion and chemotactic pseudopod protrusion to Col IV.

Antibodies, Monoclonal↗
PubMed2006

The established intimin receptor Tir and the putative eucaryotic intimin receptors nucleolin and beta1 integrin localize at or near the site of enterohemorrhagic Escherichia coli O157:H7 adherence to enterocytes in vivo.

For enterohemorrhagic Escherichia coli (EHEC) O157:H7 to adhere tightly to the intestinal epithelium and produce attach and efface (A/E) lesions, the organism must express the adhesin intimin and insert the bacterially encoded translocated intimin receptor Tir into the plasma membrane of the host enterocyte. Additionally, some reports based on tissue culture experiments indicate that intimin has affinity for the eucaryotic proteins nucleolin and beta1 integrin. To address the potential biological relevance of these eucaryotic proteins in the infection process in vivo, we sought to compare the proximity of Tir, nucleolin, and beta1 integrin to regions of EHEC O157:H7 attachment in intestinal sections from three different inoculated animals: piglets, neonatal calves, and mice. Piglets and neonatal calves were chosen because intimin-mediated adherence of EHEC O157:H7 and subsequent A/E lesion formation occur at high levels in these animals. Mice were selected because of their ease of manipulation but only after we first demonstrated that in competition with the normal mouse gut flora, an EHEC O157:H7 strain with a nonpolar deletion in the intimin gene was cleared faster than strains that produced wild-type or hybrid intimin. In all three animal species, we noted immunostained Tir beneath and stained nucleolin closely associated with adherent bacteria in intestinal sections. We also observed immunostained beta1 integrin clustered at locations of bacterial adherence in porcine and bovine tissue. These findings indicate that nucleolin and beta1 integrin are present on the luminal surface of intestinal epithelia and are potentially accessible as receptors for intimin during EHEC O157:H7 infection.

Adhesins, Bacterial↗
PubMed1998

Reciprocal interactions between beta1-integrin and epidermal growth factor receptor in three-dimensional basement membrane breast cultures: a different perspective in epithelial biology.

Anchorage and growth factor independence are cardinal features of the transformed phenotype. Although it is logical that the two pathways must be coregulated in normal tissues to maintain homeostasis, this has not been demonstrated directly. We showed previously that down-modulation of beta1-integrin signaling reverted the malignant behavior of a human breast tumor cell line (T4-2) derived from phenotypically normal cells (HMT-3522) and led to growth arrest in a three-dimensional (3D) basement membrane assay in which the cells formed tissue-like acini (14). Here, we show that there is a bidirectional cross-modulation of beta1-integrin and epidermal growth factor receptor (EGFR) signaling via the mitogen-activated protein kinase (MAPK) pathway. The reciprocal modulation does not occur in monolayer (2D) cultures. Antibody-mediated inhibition of either of these receptors in the tumor cells, or inhibition of MAPK kinase, induced a concomitant down-regulation of both receptors, followed by growth-arrest and restoration of normal breast tissue morphogenesis. Cross-modulation and tissue morphogenesis were associated with attenuation of EGF-induced transient MAPK activation. To specifically test EGFR and beta1-integrin interdependency, EGFR was overexpressed in nonmalignant cells, leading to disruption of morphogenesis and a compensatory up-regulation of beta1-integrin expression, again only in 3D. Our results indicate that when breast cells are spatially organized as a result of contact with basement membrane, the signaling pathways become coupled and bidirectional. They further explain why breast cells fail to differentiate in monolayer cultures in which these events are mostly uncoupled. Moreover, in a subset of tumor cells in which these pathways are misregulated but functional, the cells could be "normalized" by manipulating either pathway.

Basement Membrane↗
PubMed2006

Conditional deletion of beta1 integrins in the intestinal epithelium causes a loss of Hedgehog expression, intestinal hyperplasia, and early postnatal lethality.

Conditional deletion of beta1 integrins in the intestinal epithelium, unlike in epidermal and mammary epithelia, of mice does not result in decreased cell adhesion and proliferation, but instead causes a profound increase in epithelial proliferation with dysplasia and polypoid structures. The increased epithelial proliferation inhibited epithelial differentiation that caused severe malnutrition and early postnatal lethality. The striking similarities between beta1 integrin-deleted mice and neonatal mice with defective Hedgehog signaling led to the discovery that Hedgehog expression was markedly reduced in the former mice. beta1 integrins were found to drive the expression of Hedgehogs in intestinal epithelial cells in an HNF-3beta (Foxa2)-dependent fashion. The expression of Tcf-4, a transcription factor known to be required for intestinal epithelial stem cell proliferation, was increased and mislocalized in the intestinal epithelia of the beta1 integrin-deleted mice and in newborn mice treated with the Hedgehog signaling inhibitor cyclopamine. This study shows that beta1 integrins are key regulators of proliferation and homeostasis in the intestine and achieve this not through anchorage-dependent effects but by generating Hh expression and signaling.

Animals↗
PubMed1999

CD44 and beta1 integrin mediate ovarian carcinoma cell adhesion to peritoneal mesothelial cells.

Epithelial cancer of the ovary spreads by implantation of tumor cells onto the mesothelial cells lining the peritoneal cavity. The aim of this study was to identify the adhesion molecules involved in the interaction of ovarian carcinoma cells with mesothelial cells. The human ovarian carcinoma cell lines SKOV3 and NIH:OVCAR5 as well as LP9 cells, a human peritoneal mesothelial cell line, were analyzed by flow cytometry for the expression of CD44 and the beta1 integrin subunit. An in vitro adhesion assay was developed whereby LP9 cells were grown as confluent monolayers, and radiolabeled ovarian carcinoma cells were monitored for their ability to adhere to the mesothelial monolayer in the presence of potential inhibitors. Each cell line was evaluated for the presence of a pericellular matrix by a particle exclusion assay. A monoclonal antibody (MAb) against the beta1 integrin subunit significantly reduced the adhesion of SKOV3 cells to LP9 cells, whereas NIH:OVCAR5 adhesion to LP9 cells was significantly inhibited by a CD44 MAb. The LP9 cells produced both hyaluronic acid (a ligand for CD44) as well as several extracellular matrix molecules (ligands for the beta1 integrin heterodimers). These results suggest that both CD44 and the beta1 integrin heterodimers may play a role in mediating the adhesion of ovarian carcinoma cells to mesothelial cells.

Antibodies, Monoclonal↗