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PubMed2006

Mesenchymal progenitor cells communicate via alpha and beta integrins with a three-dimensional collagen type I matrix.

BACKGROUND/AIMS: The aim of our study was to investigate interactions of mesenchymal progenitor cells (MPCs) with collagen matrices. METHODS: Human bone-marrow-derived MPCs were cultivated in collagen type I gels with and without inhibition of beta(1)-integrin by a specific antibody. Collagen gel contraction, cell morphology, expression of integrin subunits and several genes related to matrix synthesis and turnover as well as MPC differentiation were analyzed over 14 days. RESULTS: Human MPCs markedly contracted free-floating collagen gels. Contraction was nearly completely inhibited by blocking beta(1)-integrin. Cellular morphology was elongated in the absence and mostly round in the presence of the antibody. Expression of integrin alpha(1), alpha(2) and beta(1) subunits showed several changes partly dependent on beta(1)-integrin blocking. Expression of matrix metalloproteinase-1 was elevated irrespective of beta(1)-integrin blocking and tenascin-C was subsequently induced during gel contraction. Spontaneous induction of chondrogenic, osteogenic or adipogenic differentiation was observed neither in the presence nor in the absence of the beta(1)-integrin antibody. CONCLUSION: Our results indicate that the interaction of human MPCs with fibrillar collagen type I involves beta(1)- and alpha-integrin subunits and induces changes in gene expression related to extracellular matrix synthesis and turnover but not differentiation to the chondrogenic, osteogenic or adipogenic phenotype.

Antibodies, Monoclonal↗

PubMed2005

Integrins in slow-cycling corneal epithelial cells at the limbus in the mouse.

Adult corneal epithelial stem cells (CESCs) have been shown to reside at the periphery of the cornea at a site called the corneoscleral junction or limbus. Although studies have shown that these cells are slow cycling, their molecular characteristics are not well understood. Using a whole-mount procedure, we show that whereas alpha9-integrin is present in a subset of the basal cells at the corneal limbus and absent in the central cornea, beta1-, beta4-, alpha3-, and alpha6-integrins are more highly expressed overall in central corneal basal cells. To characterize CESCs based on their slow-cycling nature, we simultaneously evaluated 5-bromo-2-deoxyuridine (BrdU) label-retaining cells (LRCs) and integrin expression (alpha9, beta1, and beta4) in a total of 1,889 cells at the limbus of adult mice that had been injected as neonates with BrdU. Whereas the LRCs were usually observed adjacent to alpha9-integrin-positive cells, most LRCs were alpha9-integrin-negative and expressed high levels of beta1- and beta4-integrin. In addition, we observed more BrdU-positive LRCs at the superior and inferior quadrants of adult mouse corneas than at the nasal and temporal quadrants, and determined that 0.94 to 3.6% of the limbal basal cells were slow cycling. We conclude from these data that the slow-cycling LRCs in the adult mouse cornea are enriched in cells that express high levels of beta1- and beta4-integrin and little alpha9-integrin.

Animals↗

PubMed1997

Cyclic strain induces reorganization of integrin alpha 5 beta 1 and alpha 2 beta 1 in human umbilical vein endothelial cells.

Cyclic strain has been shown to modulate endothelial cell (EC) morphology, proliferation, and function. We have recently reported that the focal adhesion proteins focal adhesion kinase (pp125FAK) and paxillin, are tyrosine phosphorylated in EC exposed to strain and these events regulate the morphological change and migration induced by cyclic strain. Integrins are also localized on focal adhesion sites and have been reported to induce by tyrosine phosphorylation of pp125FAK under a variety of stimuli. To study the involvement of different integrins in signaling induced by cyclic strain, we first observed the redistribution of alpha and beta integrins in EC subjects to 4 h cyclic strain. Human umbilical vein endothelial cells (HUVEC) seeded on either fibronectin or collagen surfaces were subjected to 10% average strain at a frequency 60 cycles/min. Confocal microscopy revealed that beta 1 integrin reorganized in a linear pattern parallel with the long axis of the elongated cells creating a fusion of focal adhesion plaques in EC plated on either fibronectin (a ligand for alpha 5 beta 1) or collagen (a ligand for alpha 2 beta 1) coated after 4 h exposure to cyclic strain. beta 3 integrin, which is a vitronectin receptor, did not redistribute in EC exposed to cyclic strain. Cyclic strain also led to a reorganization of alpha 5 and alpha 2 integrins in a linear pattern in HUVEC seeded on fibronectin or collagen, respectively. The expression of integrins alpha 5, alpha 2, and beta 1 did not change even after 24 h exposure to strain when assessed by immunoprecipitation of these integrins. Cyclic strain-induced tyrosine phosphorylation of pp125FAK occurred concomitant with the reorganization of beta 1 integrin. We concluded that alpha 5 beta 1 and alpha 2 beta 1 integrins play an important role in transducing mechanical stimuli into intracellular signals.

Cell Adhesion Molecules↗

PubMed1996

Role of MacMARCKS in integrin-dependent macrophage spreading and tyrosine phosphorylation of paxillin.

The cellular function of the MARCKS family of protein kinase C substrates is unknown. In this report, we present evidence that indicates a role for MacMARCKS, a member of the MARCKS family, in the integrin-dependent signal transduction pathways in macrophages. Using a dominant negative mutant of MacMARCKS, we showed that MacMARCKS participates in several integrin-dependent macrophage functions, including the phorbol ester-stimulated macrophage spreading, a process involving multiple integrins. The dominant negative mutant also blocks macrophage spreading on immune complex-coated surfaces, a process again requiring beta2 integrin. More direct evidence of the role of MacMARCKS in the integrin-dependent pathway is the ablation of macrophage binding to complement iC3b-coated sheep erythrocytes by MacMARCKS mutant, suggesting an effect of this mutant on the avidity of complement receptor 3, a member of the beta2 integrin family. To further evaluate the possible mechanism of MacMARCKS function, the integrin-dependent tyrosine phosphorylation of paxillin was examined. Concomitant with the inhibition of macrophage spreading and rosette formation, MacMARCKS mutant also inhibits integrin-dependent tyrosine phosphorylation of paxillin. Furthermore, immunofluorescent microscopy data showed that MacMARCKS and paxillin colocalize in the membrane ruffles at the leading edge of the spreading cells, providing a potential site and opportunity for MacMARCKS to participate in the regulation of integrin-dependent tyrosine phosphorylation of paxillin. Together, these data strongly suggest that MacMARCKS plays a role in integrin-dependent signal transduction pathways in macrophages.

Amino Acid Sequence↗

PubMed1999

Quantitative relationship among integrin-ligand binding, adhesion, and signaling via focal adhesion kinase and extracellular signal-regulated kinase 2.

Because integrin-mediated signals are transferred through a physical architecture and synergistic biochemical network whose properties are not well defined, quantitative relationships between extracellular integrin-ligand binding events and key intracellular responses are poorly understood. We begin to address this by quantifying integrin-mediated FAK and ERK2 responses in CHO cells for varied alpha(5)beta(1) expression level and substratum fibronectin density. Plating cells on fibronectin-coated surfaces initiated a transient, biphasic ERK2 response, the magnitude and kinetics of which depended on integrin-ligand binding properties. Whereas ERK2 activity initially increased with a rate proportional to integrin-ligand bond number for low fibronectin density, the desensitization rate was independent of integrin and fibronectin amount but proportional to the ERK2 activity level with an exponential decay constant of 0.3 (+/- 0.08) min(-1). Unlike the ERK2 activation time course, FAK phosphorylation followed a superficially disparate time course. However, analysis of the early kinetics of the two signals revealed them to be correlated. The initial rates of FAK and ERK2 signal generation exhibited similar dependence on fibronectin surface density, with both rates monotonically increasing with fibronectin amount until saturating at high fibronectin density. Because of this similar initial rate dependence on integrin-ligand bond formation, the disparity in their time courses is attributed to differences in feedback regulation of these signals. Whereas FAK phosphorylation increased to a steady-state level as new integrin-ligand bond formation continued during cell spreading, ERK2 activity was decoupled from the integrin-ligand stimulus and decayed back to a basal level. Accordingly, we propose different functional metrics for representing these two disparate dynamic signals: the steady-state tyrosine phosphorylation level for FAK and the integral of the pulse response for ERK2. These measures of FAK and ERK2 activity were found to correlate with short term cell-substratum adhesivity, indicating that signaling via FAK and ERK2 is proportional to the number of integrin-fibronectin bonds.

Animals↗

PubMed2000

Synergistic adhesive interactions and signaling mechanisms operating between platelet glycoprotein Ib/IX and integrin alpha IIbbeta 3. Studies in human platelets ans transfected Chinese hamster ovary cells.

This study investigates three aspects of the adhesive interaction operating between platelet glycoprotein Ib/IX and integrin alpha(IIb)beta(3). These include the following: 1) examining the sufficiency of GPIb/IX and integrin alpha(IIb)beta(3) to mediate irreversible cell adhesion on immobilized von Willebrand factor (vWf) under flow; 2) the ability of the vWf-GPIb interaction to induce integrin alpha(IIb)beta(3) activation independent of endogenous platelet stimuli; and 3) the identification of key second messengers linking the vWf-GPIb/IX interaction to integrin alpha(IIb)beta(3) activation. By using Chinese hamster ovary cells transfected with GPIb/IX and integrin alpha(IIb)beta(3), we demonstrate that these receptors are both necessary and sufficient to mediate irreversible cell adhesion under flow, wherein GPIb/IX mediates cell tethering and rolling on immobilized vWf, and integrin alpha(IIb)beta(3) mediates cell arrest. Moreover, we demonstrate direct signaling between GPIb/IX and integrin alpha(IIb)beta(3). Studies on human platelets demonstrated that vWf binding to GPIb/IX is able to induce integrin alpha(IIb)beta(3) activation independent of endogenous platelet stimuli under both static and physiological flow conditions (150-1800 s(-)(1)). Analysis of the key second messengers linking the vWf-GPIb interaction to integrin alpha(IIb)beta(3) activation demonstrated that the first step in the activation process involves calcium release from internal stores, whereas transmembrane calcium influx is a secondary event potentiating integrin alpha(IIb)beta(3) activation.

Adenosine Diphosphate↗

PubMed2001

Marching at the front and dragging behind: differential alphaVbeta3-integrin turnover regulates focal adhesion behavior.

Integrins are cell-substrate adhesion molecules that provide the essential link between the actin cytoskeleton and the extracellular matrix during cell migration. We have analyzed alphaVbeta3-integrin dynamics in migrating cells using a green fluorescent protein-tagged beta3-integrin chain. At the cell front, adhesion sites containing alphaVbeta3-integrin remain stationary, whereas at the rear of the cell they slide inward. The integrin fluorescence intensity within these different focal adhesions, and hence the relative integrin density, is directly related to their mobility. Integrin density is as much as threefold higher in sliding compared with stationary focal adhesions. High intracellular tension under the control of RhoA induced the formation of high-density contacts. Low-density adhesion sites were induced by Rac1 and low intracellular tension. Photobleaching experiments demonstrated a slow turnover of beta3-integrins in low-density contacts, which may account for their stationary nature. In contrast, the fast beta3-integrin turnover observed in high-density contacts suggests that their apparent sliding may be caused by a polarized renewal of focal contacts. Therefore, differential acto-myosin-dependent integrin turnover and focal adhesion densities may explain the mechanical and behavioral differences between cell adhesion sites formed at the front, and those that move in the retracting rear of migrating cells.

Cells, Cultured↗

PubMed2000

Vascular expression of the alpha(v)beta(3)-integrin in lung and other organs.

The expression of the alpha(v)beta(3)-integrin in nonproliferating vascular beds remains unclear. To determine possible organ-specific differences, we compared alpha(v)beta(3)-integrin expression in the lung and other organs. Paraffin-embedded tissue sections of lung, liver, brain, muscle and skin obtained from rats were processed for immunohistochemistry with a monoclonal (LM609) and a polyclonal antibody (AB1903) against the alpha(v)beta(3)-integrin. Immunogold electron microscopy was used to localize alpha(v)beta(3)-integrin in rat lung microvasculature. With the use of custom-designed primers, lung sections were subjected to in situ PCR in a thermal cycler to amplify alpha(v) or beta(3) mRNA. To confirm specific amplification, PCR products were further hybridized in situ with an alpha(v) or beta(3) cDNA probe. In the lung, the alpha(v)beta(3)-integrin protein as well as alpha(v) and beta(3) mRNAs was extensively evident in the endothelium of extra-alveolar and alveolar microvessels, in vascular smooth muscle, and in large bronchial epithelium but not in the epithelium of alveolar ducts or alveoli. Ultrastructural immunogold labeling showed the presence of the integrin on the luminal and abluminal faces of the lung microvascular endothelium but not on the apical surface of the alveolar epithelium. Staining for the integrin was generally negative in blood vessels of several systemic organs, although weak staining was evident in branches of the hepatic portal vein. The constitutive presence of the alpha(v) and beta(3) mRNAs and the alpha(v)beta(3)-integrin in the lung microvascular bed suggests that gene transcription for the integrin is ongoing in lung vessels. Because it binds vitronectin, the lung vascular alpha(v)beta(3)-integrin may play a role in ligation of bloodborne, vitronectin-containing macromolecular complexes formed in inflammation.

Animals↗

PubMed2004

Regulation of trophoblast beta1-integrin expression by contact with endothelial cells.

BACKGROUND: In human and non-human primates, migratory trophoblasts penetrate the uterine epithelium, invade uterine matrix, and enter the uterine vasculature. Invasive trophoblasts show increased expression of beta1 integrin. Since trophoblast migration within the uterine vasculature involves trophoblast attachment to endothelial cells lining the vessel walls, this raises the possibility that cell-cell contact and/or factors released by endothelial cells could regulate trophoblast integrin expression. To test this, we used an in vitro system consisting of early gestation macaque trophoblasts co-cultured on top of uterine microvascular endothelial cells. RESULTS: When cultured alone, trophoblasts expressed low levels of beta1 integrin as determined by quantitative immunofluorescence microscopy. When trophoblasts were cultured on top of endothelial cells for 24 h, the expression of trophoblast beta1 integrin was significantly increased as determined by image analysis. beta1 Integrin expression was not increased when trophoblasts were cultured with endothelial cell-conditioned medium, suggesting that upregulation requires direct contact between trophoblasts and endothelial cells. To identify endothelial cell surface molecules responsible for induction of trophoblast integrin expression, trophoblasts were cultured in dishes coated with recombinant platelet endothelial cell adhesion molecule-1 (PECAM-1), intercellular adhesion molecule-1 (ICAM-1), or alphaVbeta3 integrin. Trophoblast beta1 integrin expression (assessed by immunofluorescence microscopy and Western blotting) was increased when PECAM-1 or alphaVbeta3 integrin, but not ICAM-1, was used as substrate. CONCLUSIONS: Direct contact between trophoblasts and endothelial cells increases the expression of trophoblast beta1 integrin.

Journal Article↗

PubMed2000

BETA 2 integrin signaling in leukocytes.

Members of the beta 2 integrin family are the dominating integrins expressed on leukocytes, and they play a major role in leukocyte cell-cell and cell-matrix adhesions during inflammation and other immune responses. Beta 2 integrins are signaling receptors, but they are also targets of and are functionally affected by intracellular signals. Accordingly, researchers usually discuss two types of signaling by beta 2 integrins (and integrins in general): transmission of signals into the cell following binding of ligands or counter-receptors to the integrins (outside-in signaling), and regulation of the avidity and conformation of integrins by signals generated by other receptors within the cell (inside-out signaling). In this review, our aim is to summarize what is known about the capacity of beta 2 integrins to generate outside-in signaling in leukocytes, in particular polymorphonuclear neutrophils. Results in the literature clearly demonstrate that one of the earliest events in beta 2 integrin signaling is activation of non-receptor tyrosine kinases, which in turn triggers downstream activation of various signaling pathways that affect different functional responses of the cell. We also discuss molecules of potential importance in beta 2 integrin signaling.

CD18 Antigens↗

PubMed1999

Subversion of monocyte functions by coxiella burnetii: impairment of the cross-talk between alphavbeta3 integrin and CR3.

Several intracellular pathogens exploit macrophages as a niche for survival and replication. The success of this strategy requires the subversion or the avoidance of microbicidal functions of macrophages. Coxiella burnetii, the agent of Q fever, is a strictly intracellular bacterium that multiplies in myeloid cells. The survival of C. burnetii may depend on the selective use of macrophage receptors. Virulent C. burnetii organisms were poorly internalized but survived successfully in human monocytes, whereas avirulent variants were efficiently phagocytosed but were also rapidly eliminated. The uptake of avirulent organisms was mediated by leukocyte response integrin (alphavbeta3 integrin) and CR3 (alphaMbeta2 integrin), as demonstrated by using specific Abs and RGD sequence-containing peptides. The phagocytic efficiency of CR3 depends on its activation via alphavbeta3 integrin and integrin-associated protein. Indeed, CR3-mediated phagocytosis of avirulent C. burnetii was abrogated in macrophages from integrin-associated protein-/- mice. In contrast, the internalization of virulent C. burnetii organisms involved the engagement of alphavbeta3 integrin but not that of CR3. The pretreatment of monocytes with virulent C. burnetii organisms prevented the CR3-mediated phagocytosis of zymosan particles and CR3 activation assessed by the expression of the 24 neo-epitope. We conclude that the virulence of C. burnetii is associated with the engagement of alphavbeta3 integrin and the impairment of CR3 activity, which probably results from uncoupling alphavbeta3 integrin from integrin-associated protein. This study describes a strategy not previously reported of phagocytosis modulation by intracellular pathogens.

Antigens, CD↗

PubMedDate not supplied

[Limited proteolysis of integrin alpha v beta3 from human placenta].

Purification of alpha v beta 3 integrin from human placenta with successive usage of two affinity sorbents--immobilized monoclonal antibodies to alpha v beta 3 integrin and immobilized RGD-containing decapeptide allowed to purify this integrin's partially degraded fraction, that was nevertheless able to interact with its ligand. During the incubation of partially degraded alpha v beta 3 integrin at 37 degrees C its further degradation went on. Addition of serine proteinase inhibitors: (phenylmethilsulfonyl fluoride, leupeptin and aprotinin) completely suppressed integrin further degradation of alpha v beta 3. In preparations of intact and partially degraded alpha v beta 3 integrin specific activity of two serine proteinases--urokinase and dipeptidilpeptidase IV--was discovered. alpha v beta 3 integrin, undergoing limited proteolysis, had lesser affinity towards RGD peptide, that intact integrin. The results show, that alpha v beta 3 integrin from human placenta co-purifies with serine proteinases. It is suggested that a definite part of functionally active alpha v beta 3 integrin, extracted from human placenta by triton X-100, forms a stable complex with serine proteinases.

Female↗

PubMed2004

Expression of alphav, alpha4, alpha5 and beta3 integrin subunits, fibronectin and vitronectin in goat peri-implantation.

Integrins are glycoprotein heterodimers located in the cell membranes that stimulate intercellular adhesion and act as extracellular matrix (ECM) protein receptors. Although integrins have been detected in the implantation sites of various species, little is known about their participation in ruminant non-invasive placentation. The objective of this study was the detection of alphav, alpha4, alpha5, beta1 and beta3 integrin subunits and of two of their ligands, fibronectin and vitronectin, to determine their participation in the caprine peri-implantation process. On Day 21 post-coitum (pc), endometrial epithelium and trophoblastic cells showed an intense alphav and beta3 integrin subunits expression and moderate staining for alpha4 and alpha5. On Day 23 pc, integrin expression decreased noticeably and only a weak staining of alpha4 and beta3 integrin subunits were observed. No beta1 integrin subunit expression was detected on either of the days studied. Fibronectin (FN) expression in trophectodermic and endometrial epithelium was weak or moderate on the days studied while vitronectin (VN) expression in the same tissues was moderate or strong on Day 21 pc but decreased on Day 23 pc. These results suggest that alphavbeta3 integrin, alpha4 and alpha5 subunits, VN and FN are expressed in caprine endometrium and blastocyst and may play a role in the cascade of the implantation process.

Animals↗

PubMed2000

Expression of alpha(v)beta6 integrin in oral leukoplakia.

The distribution of alpha(v)beta6 integrin was examined in oral leukoplakia, lichen planus and squamous cell carcinomas using immunohistochemistry. Controls included oral mucosal wounds, chronically inflamed and normal oral mucosa. Integrins beta1, beta3, beta4, beta5, fibronectin and tenascin were also studied. The integrin alpha(v)beta6 was highly expressed throughout the whole lesion of 90% of the squamous cell carcinomas but was not present in any of the normal specimens. alpha(v)beta6 integrin was also expressed in 41% of the leukoplakia specimens, and 85% of the lichen planus samples, but in none of the tissues with inflammatory hyperplasia or chronic inflammation. The expression of beta1 integrins was localized in the basal layer, and that of the beta4 at the cell surface facing the basement membrane of all specimens. The integrins beta3 and beta5 were absent from all normal and leukoplakia specimens. Fibronectin and tenascin were present in the connective tissue underneath the epithelium of all the sections, and their expression was similar in both alpha(v)beta6-positive and alpha(v)beta6-negative tissues. A group of 28 leukoplakia patients were followed 1-4 years after first diagnosis. In this group, initially alpha(v)beta6 integrin-positive leukoplakia specimens had high tendency for disease progression while alpha(v)beta6-negative specimens did not progress. These results suggest that the expression of alpha(v)beta6 integrin could be associated in the malignant transformation of oral leukoplakias.

Antibodies, Monoclonal↗

PubMed2001

Transmembrane-4 superfamily proteins associate with activated protein kinase C (PKC) and link PKC to specific beta(1) integrins.

Translocation of conventional protein kinases C (PKCs) to the plasma membrane leads to their specific association with transmembrane-4 superfamily (TM4SF; tetraspanin) proteins (CD9, CD53, CD81, CD82, and CD151), as demonstrated by reciprocal co-immunoprecipitation and covalent cross-linking experiments. Although formation and maintenance of TM4SF-PKC complexes are not dependent on integrins, TM4SF proteins can act as linker molecules, recruiting PKC into proximity with specific integrins. Previous studies showed that the extracellular large loop of TM4SF proteins determines integrin associations. In contrast, specificity for PKC association probably resides within cytoplasmic tails or the first two transmembrane domains of TM4SF proteins, as seen from studies with chimeric CD9 molecules. Consistent with a TM4SF linker function, only those integrins (alpha(3)beta(1), alpha(6)beta(1), and a chimeric "X3TC5" alpha(3) mutant) that associated strongly with tetraspanins were found in association with PKC. We propose that PKC-TM4SF-integrin structures represent a novel type of signaling complex. The simultaneous binding of TM4SF proteins to the extracellular domains of the integrin alpha(3) subunit and to intracellular PKC helps to explain why the integrin alpha3 extracellular domain is needed for both intracellular PKC recruitment and PKC-dependent phosphorylation of the alpha(3) integrin cytoplasmic tail.

Animals↗

PubMed2004

Integrin expression in cells of the intervertebral disc.

In this study, we investigated the profile of integrin expression in human and porcine intervertebral disc tissue. Differences in extracellular matrix composition between anulus fibrosus (AF) and nucleus pulposus (NP) regions of the disc, as well as differences in cellular responses to environmental stimuli, suggest a role for integrins in presenting matrix signals that may mediate these responses. Human disc tissue and porcine AF and NP tissue were stained with antibodies to alpha integrin subunits 1-6, V and IIb, and beta integrin subunits 1-6 and graded for evidence of positive staining on a scale from 0 (no staining) to 3 (high incidence of staining). Human tissue expressed alpha and beta integrin subunits shown to be present in articular cartilage, including alpha(1), alpha(5) and alpha(V). Porcine AF tissue expressed similar integrin subunits to human disc, with both expressing alpha(1), alpha(5), beta(1), beta(3) and beta(5) subunits, whereas porcine NP tissue expressed higher levels of alpha(6), beta(1) and beta(4) than AF tissue. The expressed subunits are known to interact with proteins including collagens, fibronectin and laminin; however, additional studies will be required to characterize the interactions of the integrin subunits with specific matrix constituents, as well as their specific involvement in regulating environmental stimuli.

Animals↗

PubMed1996

Modulation of alpha 4 beta 1 and alpha 5 beta 1 integrin expression: heterogeneous effects of Q-switched ruby, Nd:YAG, and alexandrite lasers on melanoma cells in vitro.

BACKGROUND AND OBJECTIVE: Integrins of the beta 1 family are cellular adhesion molecules that play an important role in cell attachment and migration by interacting with extracellular matrix molecules. Agents such as hormones, cytokines, and ultraviolet radiation have all been shown to have an integrin modulating potential. The present study indicates that radiation of Q-switched lasers is also able to induce transient changes in integrin expression levels on human melanoma cells in vitro. STUDY DESIGN/MATERIALS AND METHODS: Radiation from Q-switched Ruby (694 nm), Alexandrite (755 nm), and Nd:YAG laser (1,064 nm) with fluences comparable to those that are generally used in treating dermatologic lesions were used to irradiate a subconfluent layer of human melanoma cells. After fixed time intervals, the cells were harvested either to analyse the integrin expression by flow cytometry or to investigate changes in cell attachment, spreading, and migration. RESULTS: It was established that all three types of laser were able to cause a significant downregulation of both the alpha 4 and the common beta 1 integrin subunit. The Alexandrite and Ruby lasers also induced a decrease in alpha 5 expression; however, the cells treated with the Nd:YAG laser showed a marked upregulation of the alpha 5 subunit. The expression of the other beta 1 integrin subunits was shown to be unaltered after laser treatment. Downregulation of the alpha 4 upregulation of the alpha 5 integrin subunit expression resulted in, respectively, decreased and increased attachment and spreading on fibronectin, the extracellular matrix ligand for both the alpha 4 beta 1 and alpha 5 beta 1 integrins. Marked upregulation of the alpha 5 subunit also resulted in a higher migration rate. CONCLUSION: Taken together, these results show that nonlethal doses of Q-switched laser radiation are able to induce changes in cellular behavior in vitro by modulating the integrin expression pattern.

Aluminum Oxide↗

PubMed2001

Unique expression pattern of the alpha6beta4 integrin and laminin-5 in human prostate carcinoma.

BACKGROUND: The alpha6beta4 integrin and its ligand, laminin-5, are essential gene products for the maintenance and remodeling of a stratified epithelium. Apparent loss of polarized alpha6beta4 integrin and laminin-5 protein expression in invasive prostate cancer as compared to normal prostate glands is known to occur. It is unknown whether these alterations occur in prostatic intraepithelial neoplasia (PIN) lesions and whether this combined defect occurs in other epithelial cancers. METHODS: Human prostate tissues containing both normal, PIN, and cancerous regions and normal and cancer tissue from breast and colon were obtained at surgery and examined for beta4 integrin and laminin-5 using standard immunofluorescence staining methods. RESULTS: Both normal prostate glands and PIN lesions contain beta4 integrin and laminin-5. Prostate carcinoma was unique in that both beta4 integrin and laminin-5 expression was uniformly absent. In contrast, the beta4 integrin and its ligand, laminin-5 were detected in all of the colon carcinoma cases and in 60% of the breast carcinomas. CONCLUSIONS: The beta4 integrin and its ligand, laminin-5 are altered during the transition of PIN lesions to invasive prostate carcinoma. These data suggest the loss of these proteins during cancer progression. In both prostate and breast carcinoma, the normal expression pattern of the beta4 integrin and laminin-5 is interrupted, in contrast to the persistent beta4 integrin and laminin-5 expression detected in colon carcinoma.

Antigens, Surface↗