SEARCH · PubMed Health

Results for “Integrin alpha6beta4”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 19 recordsLinked to original sources

PubMed2005

Integrin alpha6beta4 promotes expression of autotaxin/ENPP2 autocrine motility factor in breast carcinoma cells.

In advanced breast carcinomas, the alpha6beta4 integrin is associated with a migratory and invasive phenotype. In our current study, we show that expression of the alpha6beta4 integrin in MDA-MB-435 breast carcinoma cells leads to increased expression of the autocrine motility factor autotaxin, as determined by Affymetrix gene chip, real-time quantitative RT-PCR and immunoblot analyses. We further demonstrate that increased autotaxin secretion from integrin alpha6beta4 expressing cells acts to enhance chemotaxis through its ability to convert lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA) and accounts for 80% of the motogenic activity of the conditioned medium. We determine that integrin alpha6beta4-dependent overexpression of autotaxin in MDA-MB-435 cells is mediated by NFAT1, but not NFAT5, through the use of siRNAs that specifically target autotaxin, integrin beta4, NFAT1 and NFAT5. Finally, we show by electrophoretic mobility shift assays that two consensus NFAT binding sites found in the autotaxin promoter strongly and specifically bind NFAT1 from integrin alpha6beta4 expressing cells. In summary, we find that the alpha6beta4 integrin potentiates autotaxin expression through the upregulation and activation of NFAT1. These observations highlight for the first time a mechanism by which NFAT transcription factors can facilitate an invasive and motile phenotype downstream of integrin alpha6beta4 signaling.

Breast Neoplasms↗

PubMed1997

The integrin alpha6beta4 functions in carcinoma cell migration on laminin-1 by mediating the formation and stabilization of actin-containing motility structures.

Functional studies on the alpha6beta4 integrin have focused primarily on its role in the organization of hemidesmosomes, stable adhesive structures that associate with the intermediate filament cytoskeleton. In this study, we examined the function of the alpha6beta4 integrin in clone A cells, a colon carcinoma cell line that expresses alpha6beta4 but no alpha6beta1 integrin and exhibits dynamic adhesion and motility on laminin-1. Time-lapse videomicroscopy of clone A cells on laminin-1 revealed that their migration is characterized by filopodial extension and stabilization followed by lamellae that extend in the direction of stabilized filopodia. A function-blocking mAb specific for the alpha6beta4 integrin inhibited clone A migration on laminin-1. This mAb also inhibited filopodial formation and stabilization and lamella formation. Indirect immunofluorescence microscopy revealed that the alpha6beta4 integrin is localized as discrete clusters in filopodia, lamellae, and retraction fibers. Although beta1 integrins were also localized in the same structures, a spatial separation of these two integrin populations was evident. In filopodia and lamellae, a striking colocalization of the alpha6beta4 integrin and F-actin was seen. An association between alpha6beta4 and F-actin is supported by the fact that alpha6beta4 integrin and actin were released from clone A cells by treatment with the F-actin- severing protein gelsolin and that alpha6beta4 immunostaining at the marginal edges of clone A cells on laminin-1 was resistant to solubilization with Triton X-100. Cytokeratins were not observed in filopodia and lamellipodia. Moreover, alpha6beta4 was extracted from these marginal edges with a Tween-40/deoxycholate buffer that solubilizes the actin cytoskeleton but not cytokeratins. Three other carcinoma cell lines (MIP-101, CCL-228, and MDA-MB-231) exhibited alpha6beta4 colocalized with actin in filopodia and lamellae. Formation of lamellae in these cells was inhibited with an alpha6-specific antibody. Together, these results indicate that the alpha6beta4 integrin functions in carcinoma migration on laminin-1 through its ability to promote the formation and stabilization of actin-containing motility structures.

Actins↗

PubMed2003

Use of RNA interference to inhibit integrin (alpha6beta4)-mediated invasion and migration of breast carcinoma cells.

The application of small interfering RNA (siRNA) oligonucleotides to silence gene expression has profound implications for the intervention of human diseases including cancer. Using this technique, we explored the possibility that the alpha6beta4 integrin, a laminin adhesion receptor with a recognized role in the invasive phenotype of many carcinomas, represents a potential therapeutic target to inhibit the migration and invasion of carcinoma cells. We found that siRNA oligonucleotides targeted to either subunit of the alpha6beta4 integrin reduced cell surface expression of this integrin and resulted in decreased invasion of MDA-MB-231 breast carcinoma cells. Interestingly, reduced alpha6beta4 expression also promoted decreased migration on non-laminin substrata indicating that this integrin can function in a ligand-independent manner. In addition, the absence of beta4 expression in these cells augmented the formation of alpha6beta1 heterodimers and increased adhesion to laminin-1. Taken together, these results substantiate the importance of the alpha6beta4 integrin in invasion and migration that has been demonstrated previously by expression of the beta4 subunit in beta4-deficient cell lines and by function blocking antibodies. Furthermore, these data suggest that the utilization of siRNA oligonucleotides to reduce the expression of the alpha6beta4 integrin may be a useful approach to prevent carcinoma cell progression.

Biotinylation↗

PubMed2000

Altered surface expression and increased turnover of the alpha6beta4 integrin in an undifferentiated carcinoma.

The integrin alpha6beta4, predominantly expressed on tissues of epithelial origin, is known to be variably expressed on carcinomas. The biochemical changes resulting in altered expression during tumor progression are unknown. We have analyzed the expression of alpha6beta4 in a multi-step mouse model of skin carcinogenesis representing normal keratinocyte, benign papilloma and malignant undifferentiated carcinoma. All cell lines expressed the alpha6 integrin exclusively as the alpha6beta4 integrin heterodimer. Analysis of this integrin by flow cytometry and immunoprecipitation of surface labeled proteins revealed that the undifferentiated carcinoma cells have an approximately 75% reduction in surface expression of the integrin as compared with the keratinocyte and papilloma cell lines. The alpha6beta4 integrin which remains expressed on the carcinoma cells is diffusely distributed in the membrane and has an approximately 2.5-fold increased biological turnover as compared with normal keratinocytes. The decreased biological half-life and the loss of polarized expression of alpha6beta4 on the carcinoma cells suggests an altered functional role for the alpha6beta4 integrin on carcinoma cells during tumor progression. These factors may contribute to the known supression of hemidesmosome structures and the increased migration phenotype associated with some epithelial carcinomas.

Animals↗

PubMed1998

Alterations in the expression of alpha6beta4 integrin and p21/WAF1/Cip1 in N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis.

Integrin alpha6beta4 is altered in many neoplastic cells, but no data exist to show this happens in esophageal neoplasms. To examine the expression of this integrin in rat esophageal tumorigenesis induced by N-nitrosomethylbenzylamine (NMBA), (alpha6 and beta4 expression was evaluated in normal esophageal epithelium, in NMBA-induced preneoplastic lesions, and in papillomas by quantitative reverse transcription (RT)-polymerase chain reaction (PCR) and immunohistochemical analysis. Because the 34 subunit of this integrin has been found to cause cell-cycle arrest by the induction of p21/WAF1/Cip1, the expression of p21/WAF1/Cip1 was also analyzed by RT-PCR. Compared with the levels in normal epithelium, the alpha6A, alpha6B, and beta4 integrin levels in esophageal papillomas were 1.9-, 2.2-, and 2.1-fold lower, respectively. RT-PCR analysis showed no significant differences in integrin levels between preneoplastic and normal samples, and northern blot analysis of the beta4 integrin produced results in agreement with the RT-PCR results. The p21/WAF1/Cip1 level was decreased 1.6-fold in preneoplastic tissues and 3.1-fold in papilloma samples when compared with the mRNA levels in normal epithelium. Immunostaining showed that alpha6beta4 integrin was localized at the basolateral surface of the basal cells in normal esophageal epithelium. In preneoplastic lesions, however, the expression of this integrin was not polarized and was expressed in basal cells as well as in suprabasal cells. Beta4 expression was significantly reduced and alpha6A expression was decreased and delocalized in papillomas. These findings suggest that alteration in alpha6beta4 integrin and p21/WAF1/Cip1 expression may be an important biomarker for tumor progression in NMBA-induced rat esophageal tumorigenesis.

Animals↗

PubMed2002

Dynamics of the alpha6beta4 integrin in keratinocytes.

The integrin alpha6beta4 has been implicated in two apparently contrasting processes, i.e., the formation of stable adhesions, and cell migration and invasion. To study the dynamic properties of alpha6beta4 in live cells two different beta4-chimeras were stably expressed in beta4-deficient PA-JEB keratinocytes. One chimera consisted of full-length beta4 fused to EGFP at its carboxy terminus (beta4-EGFP). In a second chimera the extracellular part of beta4 was replaced by EGFP (EGFP-beta4), thereby rendering it incapable of associating with alpha6 and thus of binding to laminin-5. Both chimeras induce the formation of hemidesmosome-like structures, which contain plectin and often also BP180 and BP230. During cell migration and division, the beta4-EGFP and EGFP-beta4 hemidesmosomes disappear, and a proportion of the beta4-EGFP, but not of the EGFP-beta4 molecules, become part of retraction fibers, which are occasionally ripped from the cell membrane, thereby leaving "footprints" of the migrating cell. PA-JEB cells expressing beta4-EGFP migrate considerably more slowly than those that express EGFP-beta4. Studies with a beta4-EGFP mutant that is unable to interact with plectin and thus with the cytoskeleton (beta4(R1281W)-EGFP) suggest that the stabilization of the interaction between alpha6beta4 and LN-5, rather than the increased adhesion to LN-5, is responsible for the inhibition of migration. Consistent with this, photobleaching and recovery experiments revealed that the interaction of beta4 with plectin renders the bond between alpha6beta4 and laminin-5 more stable, i.e., beta4-EGFP is less dynamic than beta4(R1281W)-EGFP. On the other hand, when alpha6beta4 is bound to laminin-5, the binding dynamics of beta4 to plectin are increased, i.e., beta4-EGFP is more dynamic than EGFP-beta4. We suggest that the stability of the interaction between alpha6beta4 and laminin-5 is influenced by the clustering of alpha6beta4 through the deposition of laminin-5 underneath the cells. This clustering ultimately determines whether alpha6beta4 will inhibit cell migration or not.

Animals↗

PubMed2005

Hypoxia stimulates carcinoma invasion by stabilizing microtubules and promoting the Rab11 trafficking of the alpha6beta4 integrin.

Hypoxia plays a key role in tumor cell survival, invasion, and metastasis. Here we show that hypoxia increases tumor cell invasion by the modulation of Rab11, an important molecule for vesicular trafficking, especially membrane protein recycling and translocation of proteins from trans-Golgi network to plasma membrane. Dominant-negative Rab11 dramatically decreased hypoxia-induced invasion of MDA-MB-231 breast carcinoma cells without affecting cell apoptosis. Hypoxia-induced Rab11 trafficking is regulated by microtubule stability, as evidenced by the findings that hypoxia increases Glu tubulin and that colchicine blocks Rab11 trafficking and invasion. Inhibition of GSK-3beta activity by hypoxia seems to be central to microtubule stabilization and invasion. In fact, expression of a dominant-negative GSK-3beta was sufficient to stimulate invasion in normoxia. One target of Rab11-mediated trafficking that contributes to invasion is the integrin alpha6beta4. Hypoxia induced a significant increase in alpha6beta4 surface expression but it had no effect on the surface expression of alpha3beta1. This increase is dependent on Rab11 and stable microtubules. In summary, we identify vesicle trafficking as a novel target of hypoxic stimulation that is important for tumor invasion.

Animals↗

PubMed1999

Binding of integrin alpha6beta4 to plectin prevents plectin association with F-actin but does not interfere with intermediate filament binding.

Hemidesmosomes are stable adhesion complexes in basal epithelial cells that provide a link between the intermediate filament network and the extracellular matrix. We have investigated the recruitment of plectin into hemidesmosomes by the alpha6beta4 integrin and have shown that the cytoplasmic domain of the beta4 subunit associates with an NH(2)-terminal fragment of plectin that contains the actin-binding domain (ABD). When expressed in immortalized plectin-deficient keratinocytes from human patients with epidermol- ysis bullosa (EB) simplex with muscular dystrophy (MD-EBS), this fragment is colocalized with alpha6beta4 in basal hemidesmosome-like clusters or associated with F-actin in stress fibers or focal contacts. We used a yeast two-hybrid binding assay in combination with an in vitro dot blot overlay assay to demonstrate that beta4 interacts directly with plectin, and identified a major plectin-binding site on the second fibronectin type III repeat of the beta4 cytoplasmic domain. Mapping of the beta4 and actin-binding sites on plectin showed that the binding sites overlap and are both located in the plectin ABD. Using an in vitro competition assay, we could show that beta4 can compete out the plectin ABD fragment from its association with F-actin. The ability of beta4 to prevent binding of F-actin to plectin explains why F-actin has never been found in association with hemidesmosomes, and provides a molecular mechanism for a switch in plectin localization from actin filaments to basal intermediate filament-anchoring hemidesmosomes when beta4 is expressed. Finally, by mapping of the COOH-terminally located binding site for several different intermediate filament proteins on plectin using yeast two-hybrid assays and cell transfection experiments with MD-EBS keratinocytes, we confirm that plectin interacts with different cytoskeletal networks.

Actins↗

PubMed2001

Traction forces mediated by alpha6beta4 integrin: implications for basement membrane organization and tumor invasion.

The integrin alpha6beta4, a laminin receptor that stabilizes epithelial cell adhesion to the basement membrane (BM) through its association with cytokeratins, can stimulate the formation and stabilization of actin-rich protrusions in carcinoma cells. An important, unresolved issue, however, is whether this integrin can transmit forces to the substrate generated by the acto-myosin system. Using a traction-force detection assay, we detected forces exerted through alpha6beta4 on either laminin-1 or on an anti-alpha6 antibody, demonstrating that this integrin can transmit forces without the need to engage other integrins. These alpha6beta4-dependent traction forces were organized into a compression machine localized to the base of lamellae. We hypothesized that the compression forces generated by alpha6beta4 result in the remodeling of BMs because this integrin plays a major role in the interaction of epithelial and carcinoma cells with such structures. Indeed, we observed that carcinoma cells are able to remodel a reconstituted BM through alpha6beta4-mediated compression forces by a process that involves the packing of BM material under the cells and the mechanical removal of BM from adjacent areas. The distinct signaling functions of alpha6beta4, which activate phosphoinositide 3-OH kinase and RhoA, also contribute to remodeling. Importantly, we demonstrate remodeling of a native BM by epithelial cells and the involvement of alpha6beta4 in this remodeling. Our findings have important implications for the mechanism of both BM organization and tumor invasion.

Antigens, Surface↗

PubMed2003

Recognition of the neural chemoattractant Netrin-1 by integrins alpha6beta4 and alpha3beta1 regulates epithelial cell adhesion and migration.

Netrins, axon guidance cues in the CNS, have also been detected in epithelial tissues. In this study, using the embryonic pancreas as a model system, we show that Netrin-1 is expressed in a discrete population of epithelial cells, localizes to basal membranes, and specifically associates with elements of the extracellular matrix. We demonstrate that alpha6beta4 integrin mediates pancreatic epithelial cell adhesion to Netrin-1, whereas recruitment of alpha6beta4 and alpha3beta1 regulate the migration of CK19+/PDX1+ putative pancreatic progenitors on Netrin-1. These results provide evidence for the activation of epithelial cell adhesion and migration by a neural chemoattractant, and identify Netrin-1/integrin interactions as adhesive/guidance cues for epithelial cells.

Animals↗

PubMed1999

Crystal structure of a tandem pair of fibronectin type III domains from the cytoplasmic tail of integrin alpha6beta4.

The integrin alpha6beta4 is an essential component of hemidesmosomes but it also plays a dynamic role in invasive carcinoma cells. The cytoplasmic tail of the beta4 subunit is uniquely large among integrins and includes two pairs of fibronectin type III domains separated by a connecting segment. Here we describe the crystal structure of the first tandem domain pair, a module that is critical for alpha6beta4 function. The structure reveals a novel interdomain interface and candidate protein-binding sites, including a large acidic cleft formed from the surfaces of both domains and a prominent loop that is reminiscent of the RGD integrin-binding loop of fibronectin. This is the first crystal structure of either a hemidesmosome component or an integrin cytoplasmic domain, and it will enable the intracellular functions of alpha6beta4 to be dissected at the atomic level.

Amino Acid Sequence↗

PubMed2003

Compartmentalization of integrin alpha6beta4 signaling in lipid rafts.

Integrin alpha6beta4 signaling proceeds through Src family kinase (SFK)-mediated phosphorylation of the cytoplasmic tail of beta4, recruitment of Shc, and activation of Ras and phosphoinositide-3 kinase. Upon cessation of signaling, alpha6beta4 mediates assembly of hemidesmosomes. Here, we report that part of alpha6beta4 is incorporated in lipid rafts. Metabolic labeling in combination with mutagenesis indicates that one or more cysteine in the membrane-proximal segment of beta4 tail is palmitoylated. Mutation of these cysteines suppresses incorporation of alpha6beta4 in lipid rafts, but does not affect alpha6beta4-mediated adhesion or assembly of hemidesmosomes. The fraction of alpha6beta4 localized to rafts associates with a palmitoylated SFK, whereas the remainder does not. Ligation of palmitoylation-defective alpha6beta4 does not activate SFK signaling to extracellular signal-regulated kinase and fails to promote keratinocyte proliferation in response to EGF. Thus, compartmentalization in lipid rafts is necessary to couple the alpha6beta4 integrin to a palmitoylated SFK and promote EGF-dependent mitogenesis.

Amino Acid Sequence↗

PubMed2004

The cAMP-Epac-Rap1 pathway regulates cell spreading and cell adhesion to laminin-5 through the alpha3beta1 integrin but not the alpha6beta4 integrin.

Laminin-5 is an important constituent of the basal lamina. The receptors for laminin-5, the integrins alpha3beta1 and alpha6beta4, have been associated with epithelial wound migration and carcinoma invasion. The signal transduction mechanisms that regulate these integrins are not well understood. We report here that the small GTPase Rap1 regulates the adhesion of a number of cell lines to various extracellular matrix proteins including laminin-5. cAMP also mediates cell adhesion and spreading on laminin-5, a process that is independent of protein kinase A but rather dependent on Epac1, a cAMP-dependent exchange factor for Rap. Interestingly, although both alpha3beta1 and alpha6beta4 mediate adhesion to laminin-5, only alpha3beta1-dependent adhesion is dependent on Rap1. These results provide evidence for a function of the cAMP-Epac-Rap1 pathway in cell adhesion and spreading on different extracellular matrix proteins. They also define different roles for the laminin-binding integrins in regulated cell adhesion and subsequent cell spreading.

Actins↗

PubMed1999

Activated Rac1 selectively up-regulates the expression of integrin alpha6beta4 and induces cell adhesion and membrane ruffles of nonadherent colon cancer Colo201 cells.

Functions of small GTPases in integrin expression were investigated when the interaction of nonadherent human colon carcinoma 201 cells with the extracellular matrix (ECM) was examined. By transfection of the constitutively active form of a small GTPase Rac1, Rac V12, adhesion of cells to the ECM increased with concomitant cell spreading and formation of membrane ruffles. Activated Cdc42 and Cdc42 V12, but not wild-type Rac1, Cdc42, or RhoA, also induced the adhesion and spreading of Colo201 cells. This adhesion is integrin beta4 dependent since an antibody for integrin beta4 inhibited the RacV12-dependent cell adhesion and numbers of adhesive cells on laminin-coated plates exceeded those on collagen- and fibronectin-coated plates. By immunofluorescence, in addition to clustering of integrin molecules, expression of integrin alpha6beta4 on the cell surface of Rac V12- and Cdc42 V12-expressing cells was selectively up-regulated without an increase in biosynthesis of alpha6beta4 integrin. Treatment of Rac V12-expressing cells with wortmannin or LY294002, specific inhibitors of phosphoinositide 3-OH kinase, decreased the up-regulated alpha6beta4 and cell adhesion. In light of this evidence, we propose that the regulation of integrin alpha6beta4 expression induced by Rac1 and Cdc42 may play an important role in cell adhesion and tumorigenesis of colon carcinoma cells.

Antibodies, Monoclonal↗

PubMed1999

Isolated deficient alpha6beta4 integrin expression in the gut associated with intractable diarrhea.

BACKGROUND: An infant born with pyloric atresia had development of intractable diarrhea and was found to have total epithelial detachment of gastric and small and large bowel mucosa. She had no skin abnormalities. Parental consanguinity and pyloric atresia in a sibling who died without autopsy suggest an inherited origin for this disorder. The purpose of this study was to examine defects in intestinal and skin cell adhesion. METHODS: Histologic, immunohistochemical, and ultrastructural characteristics of the skin and gut of the patient were compared with that of normal control subjects. Distribution of adhesion molecules was determined. RESULTS: Immunofluorescent analysis of the digestive mucosa showed alpha6beta4 integrin expression deficiency at the epithelial cell-lamina propria junction. Ultrastructural examination of the digestive mucosa revealed a complete epithelial detachment with a cleavage plane lying between the lamina densa and the basal pole of the enterocytes. Consistent with the absence of skin blistering, integrin alpha6beta4 was expressed at the dermal-epidermal junction. Electron micrographs of skin biopsy specimens showed the presence of normal hemidesmosomes and the absence of dermal-epidermal dysadhesion. CONCLUSION: It was postulated that this patient had protracted diarrhea related to epithelial detachment of the digestive mucosa as a consequence of a deficiency of an integrin alpha6beta4 isoform specific to the gut.

Antigens, Surface↗

PubMed2003

Transforming growth factor-beta-inducible gene-h3 (beta(ig)-h3) promotes cell adhesion of human astrocytoma cells in vitro: implication of alpha6beta4 integrin.

Beta(ig)-h3 is a secretory protein that is induced by transforming growth factor (TGF)-beta. We have recently found that beta(ig)-h3 expression is induced in cultured astrocytes by TGF-beta1 and in rat cerebral cortex by stab wound. The purpose of this study was to examine the effect of the secreted beta(ig)-h3 on cell adhesion of astrocytes and the underlying mechanisms. When U87 human astrocytoma cells were seeded on dishes coated with recombinant beta(ig)-h3, cell adhesion was significantly enhanced. Blocking experiments using various antibodies to the integrin subunit suggested alpha6beta4 integrin could be involved in the beta(ig)-h3-mediated astrocyte cell adhesion. Cell adhesion to beta(ig)-h3 substrate was substantially blocked by preincubation with the inhibitor to the src kinase. When cells were plated on beta(ig)-h3-coated dishes, tyrosine phosphorylation of focal adhesion kinase was prominently increased within 20 min in a beta4 integrin-dependent manner. The results suggest that alpha6beta4 integrin-mediated interactions of astrocytes with beta(ig)-h3 transduce intracellular signals through the focal adhesion proteins, which may regulate certain aspects of astrocyte response to brain injury.

Astrocytoma↗

PubMed2004

Chromogenic in situ hybridization for alpha6beta4 integrin in breast cancer: correlation with protein expression.

The alpha6beta4 integrin is the receptor for the basement membrane protein laminin-5. Recent studies suggest that alpha6beta4 integrin expression in invasive breast carcinomas may be a poor prognostic factor. Because we have not had reliable results with commercially available antibodies for the immunohistochemical detection of alpha6beta4 integrin in archival paraffin-embedded tissues, we designed a probe to detect beta4 integrin subunit mRNA in paraffin sections. In situ hybridization for beta4 mRNA was performed on paraffin-embedded tissue sections of 25 invasive breast carcinomas using a hyperbiotinylated oligonucleotide DNA probe. Immunohistochemical staining was performed on corresponding frozen tumor sections using two commercially available antibodies to the beta4 integrin subunit. All cases positive for beta4 protein by one or both antibodies were also positive for beta4 mRNA by in situ hybridization, but three cases with beta4 mRNA expression were negative by immunohistochemistry with both antibodies. These findings suggest that in situ hybridization appears to be a sensitive method for detecting beta4 integrin mRNA, but it appears to identify some cases that either lack beta4 protein or express variants not recognized with commercial antibodies directed to particular extracellular or cytoplasmic domains.

Adult↗

PubMedDate not supplied

Expression of the alpha6beta4 integrin provides prognostic information in bladder cancer.

Integrins are cell surface receptors for extracellular matrix components that may participate in metastatic processes. Normal urothelial tissues show a polarized expression of alpha6beta4 integrin on basal cells at their junction with the lamina propria. We have previously shown that bladder cancers frequently overexpress one member of the integrin family, the alpha6beta4 integrin. In this study, we evaluated the level of alpha6beta4 integrin expression in bladder cancer specimens from 57 patients and correlated the expression level with patient survival. Expression was evaluated by immunoperoxidase staining. Three patterns of alpha6beta4 expression were observed: negative (13 patients); strong overexpression throughout the tumor cells (21 patients); and weak expression that most closely resembled expression in normal urothelium (23 patients). Individuals with weak staining tumors had a statistically significantly better survival (p=0.041) than patients whose tumors exhibited either no expression or strong overexpression. These data indicate that evaluation of the expression of alpha6beta4 integrin may provide valuable prognostic information on clinical outcome in patients with bladder cancer.

Antigens, Surface↗