Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Integrin alpha Chains”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 289 records · Page 16Linked to original sources
PubMed1996

Osteopontin N-terminal domain contains a cryptic adhesive sequence recognized by alpha9beta1 integrin.

Osteopontin is an adhesive glycoprotein implicated in numerous diseases associated with inflammation and remodeling. There are several structural domains in osteopontin that are of particular interest. The RGD motif is a cell attachment sequence shown to be critical for cell adhesion through alphav-containing integrins. In close proximity to the RGD domain is the thrombin cleavage site. Previous observations suggest that thrombin cleavage of osteopontin occurs in vivo and may be physiologically important. To study the functional significance of osteopontin cleavage by thrombin, we made glutathione S-transferase-osteopontin fusion proteins. These proteins contain either the N- or C-terminal domains expected to be formed following thrombin cleavage at the Arg169-Ser170 peptide bond. We compared these osteopontin fragments with native osteopontin in their ability to support adhesion of several different cell lines and identified the receptors mediating these interactions. Our data show that the N-terminal osteopontin fragment, which contains the RGD domain, supports adhesion of a melanoma cell line that is unable to bind native osteopontin. This suggests that osteopontin adhesive interactions may be regulated by thrombin cleavage. We also demonstrate that osteopontin contains a cryptic binding activity, which can be recognized by a novel osteopontin receptor. This receptor has been identified as the alpha9beta1 integrin.

Animals↗
PubMed1997

The epithelial cell-specific integrin, CD103 (alpha E integrin), defines a novel subset of alloreactive CD8+ CTL.

The interaction of CD8+CTL with epithelial layers is an important but poorly defined aspect of organ allograft rejection. We herein report that CD103 (formerly alpha E integrin), a known receptor for the epithelial cell-specific ligand E-cadherin, is expressed by a major subset of CD8 + CTL elicited in response to allogeneic renal epithelial cells (REC). In contrast, CD103 was expressed poorly on CD8 + CTL generated in the conventional manner by stimulation with allogeneic leukocytes, although expression could be dramatically up-regulated by supplementing cultures with REC or exogenous TGF-beta 1. That TGF-beta controls the expression of CD103 on CD8+ CTL was further supported by the capacity of anti-TGF-beta mAb to block the generation of such cells in anti-REC cultures. Clonal analyses of anti-REC cultures revealed that individual CD8+ CTL clones were discretely CD103+ or CD103-, nd maintained their respective phenotypes independently of the cell type used for clonal restimulation. In a mouse model of graft-vs-host disease, 16.4 +/- 2.7% of CD8 cells that infiltrated host kidneys were CD103+ (n = 4). CD8 kidney-infiltrating lymphocytes were predominantly of donor origin and displayed an activated/memory phenotype (CD62L-, CD44high), consistent with expression of CD103 on a CD8 effector subset elicited in vivo following allogeneic transplantation. Taken together, the present data demonstrate that CD103 identifies a novel CD8 effector subset and, moreover, that such cells may comprise a significant component of the response to allogeneic tissues. The potential for CD103+ CTL as an important effector mechanism in organ allograft rejection, and more generally, as a mechanistic basis for tissue-specific immune phenomena, is discussed.

Animals↗
PubMed1998

Expansion of the nonadherent myeloid cell population by monoclonal antibodies against tenascin-C in murine long-term bone marrow cultures.

Tenascin-C, a predominantly mesenchymal extracellular matrix protein, has a restricted distribution in adult tissues. It has previously been shown that this protein is expressed in the bone marrow. In this paper we show that murine myeloid and lymphoid long-term bone marrow cultures differ in their expression of tenascin-C splice variants. In the adherent stromal layer of myeloid cultures, the 260-kDa polypeptide encoded by the 8-kb mRNA was the major splice variant, whereas in the stromal layer of lymphoid cultures both the shorter 210-kDa polypeptide encoded by the 6-kb mRNA and the 260-kDa polypeptide were abundantly expressed. However, in both culture systems the larger 260-kDa tenascin-C polypeptide was the major isoform secreted in the culture supernatant. This finding is in agreement with previous reports indicating that the smaller 210-kDa isoform is preferentially deposited in the stroma, whereas the alternatively spliced segment in the 260-kDa tenascin-C may contain anti-adhesive domains. Glucocorticoids in myeloid long-term bone marrow cultures and in the MC3T3-G2/PA6 cell line downregulated the expression of tenascin-C. In the present study we observed that this was due primarily to downregulation of the 8-kb major splice variant of the tenascin-C mRNA. We also studied the possible role of tenascin-C in the bone marrow by using antibodies against tenascin-C in long-term bone marrow cultures. We found that three monoclonal antibodies against the carboxyterminal type III fibronectin repeats of tenascin-C (TNCfn 7-8) increased the number of the non-adherent myeloid cells in myeloid long-term bone marrow cultures. It has recently been suggested that the TNCfn 6-8 domain of tenascin-C binds to the alpha8beta1 integrin. Using Northern blotting, we found that the integrin alpha8 subunit was expressed in adherent cells in bone marrow cultures, raising the possibility that tenascin-C acts in bone marrow cultures by binding to the alpha8beta1 integrin.

Animals↗
PubMed1998

Retroviral transfer of antisense integrin alpha6 or alpha8 sequences results in laminar redistribution or clonal cell death in developing brain.

To assess the roles of two integrin alpha subunits (alpha6 and alpha8) in the developing chicken optic tectum, progenitors were infected with retroviral vectors that contained the marker gene lacZ plus antisense sequences from either the alpha6 or alpha8 integrin subunit cDNAs. On embryonic day 3 (E3), the vector was injected into tectal ventricles of chicken embryos. On E6, E7.5, E9, or later, chicken embryos were killed, and optic tecta were dissected and processed for histochemical detection of lacZ-positive cells. The antisense-bearing cell clones (descendants of a single infected progenitor) were analyzed for proliferation and migration patterns and were compared with lacZ-only vector-infected control clones. At E6, both alpha6 and alpha8 integrin antisense-containing cell clones were similar to controls. At E7.5, integrin alpha8 antisense-containing clones exhibited a cell number reduction in upper laminae (intermediate zone and tectal plate), and at E9, they exhibited a reduction in the ventricular zone as well. Integrin alpha6 antisense-containing cell clones exhibited no difference in total cell number at E9 but had a net laminar redistribution of more cells in the ventricular zone and less cells in the tectal plate. Our data show that different integrins play different roles during brain development: alpha6 integrin is essential for migration of tectal cells into specific laminae, and alpha8 integrin is essential for the survival of optic tectum cells. Also alpha8 integrin-substrate interactions may suppress early programmed cell death in premigratory and migratory neuroblasts.

Animals↗
PubMed1998

Enrichment of T cells carrying beta7 integrins in inflamed synovial tissue from patients with early spondyloarthropathy, compared to rheumatoid arthritis.

OBJECTIVE: To compare the expression of adhesion molecules on synovial T cells from patients with early spondyloarthropathy (SpA) and rheumatoid arthritis (RA), with special reference to the beta7 integrins alpha4beta7 and alphaEbeta7 in view of their intimate association with intestinal tissue. METHODS: Twenty-five synovial cell lines were generated by interleukin 2 (IL-2) expansion from synovial biopsies of patients with early SpA and RA, obtained from macroscopically inflamed synovial tissue by needle arthroscopy, and subsequently characterized by flow cytometry for CD3, CD4, CD8, L-selectin, CD11a, CD31, CD44, and alpha4beta7 and alphaEbeta7 integrin. RESULTS: In SpA, the beta7 integrin expression was increased, compared to RA. Furthermore, an inverse relation between alpha4beta7 and alphaEbeta7 was present in SpA (r = -0.75, p < 0.02), as on many mucosal T cells. In contrast, an opposite correlation was noted in RA (r = +0.84, p < 0.01), as similarly described on a subset of circulating T cells. CONCLUSION: Increased expression of beta7 integrins was noted on synovial T cell lines from SpA compared to RA, with discriminative correlations between alpha4beta7 and alphaEbeta7. This suggests a different origin of the synovial T cells in these diseases.

Adolescent↗
PubMed1997

Importance of the tubulointerstitium in human glomerulonephritis. II. Distribution of integrin chains beta 1, alpha 1 to 6 and alpha V.

Accumulation of extracellular matrix is important in the progression of glomerulonephritis. Since adherent cell types utilize integrins to bind and organize extracellular matrix proteins, we have assessed expression of the beta 1 integrins in sequential sections from 85 human renal biopsies and 4 normal kidneys by immunohistochemical staining. Our results demonstrate strong correlations between expression of the alpha 5 chain within the interstitium, the alpha V chain on proximal and distal tubular epithelium and the presence of chronic histological damage. Moreover, staining for interstitial alpha 5 and proximal and distal tubular alpha V were also strongly associated with expression of certain adhesion molecules (ICAM-1, VCAM-1, E-selectin and L-selectin) and the presence of macrophages within the interstitium, which have been linked, in an earlier study, with the degree of chronic histological damage and disease progression. However, in contrast to our earlier study of adhesion molecules, there were also associations between expression of integrin chains within the glomerulus and tubulointerstitium. For example, there were strong positive associations between staining for alpha 5 on glomerular endothelium and its expression on extraglomerular vascular endothelium and between both mesangial alpha 1 and podocyte alpha 3 and tubular staining for the common beta 1 subunit. While the functional significance of these associations is obscure, they suggest some kind of communication between cells in different sites in the kidney. There were also positive associations between staining for different integrins within the glomerulus, notably mesangial cell staining for alpha 2, glomerular endothelial cells staining for alpha 5 and glomerular epithelial cell alpha 3. These results suggest that there is a coordinated upregulation of integrin expression both within the tubulointerstitium and the glomerulus and that at least some of these integrins (interstitial alpha 5 and distal tubular alpha V) are associated with the expression of other adhesion molecules, macrophage infiltration and the presence of markers of disease progression (interstitial fibrosis and tubular atrophy).

Antigens, CD↗
PubMed1995

Appearance and distribution of laminin A chain isoforms and integrin alpha 2, alpha 3, alpha 6, beta 1, and beta 4 subunits in the developing human small intestinal mucosa.

BACKGROUND: Laminin, a major component of basement membranes, is well known in its classical heterotrimeric form (B1-A-B2) to regulate diverse biological functions, including cell polarization and differentiation. However, the role of merosin, a laminin-like molecule in which an M chain is substituted for its homologous A chain, remains largely unknown. METHODS: In the present study, we analyzed by indirect immunofluorescence the expression and distribution of these four laminin chains as well as the integrins alpha 2 beta 1, alpha 3 beta 1, alpha 6 beta 1, and alpha 6 beta 4, four potential receptors, at the epithelial-mesenchymal interface of the developing human small intestine, with a panel of specific monoclonal antibodies. RESULTS: Beginning at 7 weeks of gestation and throughout mucosal organogenesis, the B1 and B2 chains were uniformly detected at the epithelial basement membrane. The A chain also was detected beginning at 7 weeks, and its distribution at the basement membrane remained uniform throughout villus (9+ weeks) and crypt (16+ weeks) formation. In contrast, M chain expression was not observed until 16 weeks; between 16 and 20 weeks, it was exclusively associated with the base of epithelial cells that comprised the forming crypts. Integrins alpha 6 beta 1 and alpha 6 beta 4, as determined by their subunit immunolocalization, appeared to be expressed by all enterocytes from 7 to 20 weeks. In contrast, the expression of the alpha 2 beta 1 and alpha 3 beta 1 integrins was found time- and site-restricted. The alpha 2 subunit was predominantly detected in the epithelial cells of the intervillous area and its derivative, the crypt, whereas the alpha 3 subunit was strongly expressed by all epithelial cells except those located at the bottom of 19-20-week-old crypts. CONCLUSIONS: Taken together, these observations demonstrate that both compositional changes in the basement membrane and differential expression of receptors occur during human intestinal organogenesis, suggesting that epithelial cell-matrix interactions play a role during development.

Antigens, CD↗
PubMed2000

The role of alpha and beta chains in ligand recognition by beta 7 integrins.

Integrins alpha(E)beta(7) and alpha(4)beta(7) are involved in localization of leukocytes at mucosal sites. Although both alpha(E)beta(7) and alpha(4)beta(7) utilize the beta(7) chain, they have distinct binding specificities for E-cadherin and mucosal addressin cell adhesion molecule-1 (MAdCAM-1), respectively. We found that mutation of the metal ion-dependent adhesion site (MIDAS) in the alpha(E) A-domain (D190A) abolished E-cadherin binding, as did mutation F298A on the A-domain surface near the MIDAS cleft. A docking model of the A-domain with E-cadherin domain 1 indicates that coordination of the alpha(E) MIDAS metal ion by E-cadherin Glu(31) and a novel projection of Phe(298) into a hydrophobic pocket on E-cadherin provide the basis for the interaction. The location of the binding site on the alpha(E) A-domain resembles that on other integrins, but its structure appears distinctive and particularly adapted to recognize the tip of E-cadherin, a unique integrin ligand. Additionally, mutation of the beta(7) MIDAS motif (D140A) abolished alpha(E)beta(7) binding to E-cadherin and alpha(4)beta(7)-mediated adhesion to MAdCAM-1, and alpha(4) chain mutations that abrogated binding of alpha(4)beta(1) to vascular cell adhesion molecule-1 and fibronectin similarly reduced alpha(4)beta(7) interaction with MAdCAM-1. Thus, although specificity can be determined by the integrin alpha or beta chain, common structural features of both subunits are required for recognition of dissimilar ligands.

Amino Acid Sequence↗
PubMed2000

Leukocyte chemosensory migration on vascular prosthetic biomaterial is mediated by an integrin beta2 receptor chain.

The ability of adherent activated leukocytes to migrate on implanted prosthetic biomaterial surfaces may be an early rate-limiting step in eliminating periprosthetic infection. The goal of this study was to explore the molecular mechanism governing leukocyte migration on the implantable cardiovascular prosthetic biomaterial, expanded polytetrafluoroethylene (ePTFE), in response to stimulation by the soluble chemokine, N-formyl-methionyl-leucyl-phenylalanine (fMLP). We used a population level migration assay to study the migration of polymorphonuclear leukocytes (PMN) on ePTFE, overlaid by a gelatin/agar composite. A theoretical random walk model was applied to describe fMLP-induced PMN migration on ePTFE in terms of an objective random cell migration coefficient, mu. Our results show that following stimulation with 0-10(-7) M fMLP, the value of mu ranged from 5.43 x 10(-9) to 1.08 x 10(-7) cm2/s, with a maximum value obtained at 10(-8) M fMLP. We probed the expression levels of various beta2 integrin receptor subunits and their contribution to the migratory function of ePTFE-adherent PMN over a wide range of fMLP concentration. We found that the expression of the integrin beta-chain, CD18, was also maximized at 10(-8) M fMLP, along with only slight changes in the expression of integrin alpha-chains (CD11a,b,c). We report that treatment with antibodies against either beta or combined alpha chains, but not individual alpha chains, inhibited PMN attachment to ePTFE at 10(-8) M fMLP, suggesting the likely role of combined beta2 receptor subunits in early adhesion events following stimulation. However, treatment with only anti-CD18 significantly lowered PMN migration on ePTFE (mu = 5.98 x 10(-9) cm2/s), and this degree of inhibition was much greater than that elicited by the combined treatment with antibodies recognizing all possible alpha-chains. Overall, we conclude that migratory behavior of chemokinetically stimulated PMN on ePTFE is mediated by the integrin beta chain pool, and is only weakly regulated by the integrin alpha chain.

Antigens, CD↗
PubMed2000

The LIM-only protein DRAL/FHL2 binds to the cytoplasmic domain of several alpha and beta integrin chains and is recruited to adhesion complexes.

LIM proteins contain one or more double zinc finger structures (LIM domains) mediating specific contacts between proteins that participate in the formation of multiprotein complexes. We report that the LIM-only protein DRAL/FHL2, with four and a half LIM domains, can associate with alpha(3A), alpha(3B), alpha(7A), and several beta integrin subunits as shown in yeast two-hybrid assays as well as after overexpression in human cells. The amino acid sequence immediately following the conserved membrane-proximal region in the integrin alpha subunits or the C-terminal region with the conserved NXXY motif of the integrin beta subunits are critical for binding DRAL/FHL2. Furthermore, the DRAL/FHL2 associates with itself and with other molecules that bind to the cytoplasmic domain of integrin alpha subunits. Deletion analysis of DRAL/FHL2 revealed that particular LIM domains or LIM domain combinations bind the different proteins. These results, together with the fact that full-length DRAL/FHL2 is found in cell adhesion complexes, suggest that it is an adaptor/docking protein involved in integrin signaling pathways.

3T3 Cells↗
PubMed1995

CD3 and CD2 ligation alters CD49d epitope expression.

The combination of anti-CD2 plus anti-CD3 monoclonal antibodies (mAbs) synergistically prolongs allograft survival and induces antigen-specific tolerance. Since altered expression of cell surface molecules might be important for tolerance induction, the effect of anti-CD2 and anti-CD3 mAbs on the expression of adhesion molecules was analyzed on splenic T cells with an in vitro model. The anti-CD2 mAb, 12-15, alone had no effect on the expression of integrin alpha 4-chain epitopes recognized by two anti-CD49d (VLA-4 alpha) mAbs, R1-2 and PS/2. The anti-CD3 mAb, 2C11, caused R1-2 epitope expression to decrease, while PS/2 epitope expression remained unchanged. The combination of anti-CD2 and anti-CD3 mAbs further decreased R1-2 epitope expression while preserving PS/2 epitope expression. The expression of integrin beta 1 and beta 7 chains, each of which form heterodimers with alpha 4 chains, also remained unchanged. Expression of other integrin, selectin, or immunoglobulin superfamily molecules (CD11a, CD18, CD44, CD45, CD48, CD54 and CD62L) were all significantly increased by anti-CD2 or anti-CD3 mAbs. Decreased R1-2 epitope expression was anti-CD3 dependent and specifically augmented by anti-CD2 mAb. CD2-regulated decreases in R1-2 epitope expression correlated with increased cAMP and could be prevented by addition of high doses of IL-2 but was not affected by the addition of other cytokines. R1-2 alpha 4 epitope expression could be specifically restored by the divalent cation Mn2+, which also increased functional binding to the VCAM-1 ligand. Significantly, the R1-2 but not the PS/2 mAb prolonged graft survival in a cardiac allograft model. These results show that anti-CD2 and anti-CD3 mAbs selectively decrease integrin alpha 4 chain epitope expression on T cells through conformational regulation. Decreased expression of a CD49d epitope is unique in comparison to the up-modulation of other T-cell adhesion receptors. These changes correlate with functional effects and provide an additional mechanistic explanation for the synergistic effect of anti-CD2 plus anti-CD3 in producing tolerance.

Animals↗
PubMed1995

Mapping of network-forming, heparin-binding, and alpha 1 beta 1 integrin-recognition sites within the alpha-chain short arm of laminin-1.

Cell-interactive and architecture-forming functions are associated with the short arms of basement membrane laminin-1. To map and characterize these functions, we expressed recombinant mouse laminin-1 alpha-chain extending from the N terminus through one third of domain IIIb. This dumbbell-shaped glycoprotein (r alpha 1(VI-IVb)'), secreted by mammalian cells, was found to possess three activities. 1) Laminin polymerization was quantitatively inhibited by recombinant protein, supporting an alpha-chain role for a three-short arm interaction model of laminin self-assembly. 2) r alpha 1(VI-IVb)' bound to heparin, and the activity was localized to a subfragment corresponding to domain VI by 125I-heparin blotting. 3) PC12 rat pheochromocytoma cells adhered to, and rapidly extended branching neurites on, r alpha 1(VI-IVb)', with adhesion inhibited by alpha 1 and beta 1 integrin chain-specific antibodies. The ability of anti-laminin antibody to block PC12 cell adhesion to laminin was selectively prevented by absorption with r alpha 1(VI-IVb)' or alpha-chain domain VI fragment. This active integrin-recognition site could furthermore be distinguished from a second cryptic alpha 1 beta 1-binding site exposed by heat treatment of fragment P1', a short arm fragment lacking globules. Thus, a polymer-forming, a heparin-binding, and the active alpha 1 beta 1 integrin-recognition site are all clustered at the end of the alpha-chain short arm, the latter two resident solely in domain VI.

Amino Acid Sequence↗
PubMed2006

Laminin alpha1 chain mediated reduction of laminin alpha2 chain deficient muscular dystrophy involves integrin alpha7beta1 and dystroglycan.

Transgenically introduced laminin (LN) alpha1 chain prevents muscular dystrophy in LNalpha2 chain deficient mice. We now report increased integrin alpha7Bbeta1D synthesis in dystrophic LNalpha2 chain deficient muscle. Yet, immunofluorescence demonstrated a reduced expression of integrin alpha7B subunit at the sarcolemma. Transgenic expression of LNalpha1 chain reconstituted integrin alpha7B at the sarcolemma. Expression of alpha- and beta-dystroglycan is enhanced in LNalpha2 chain deficient muscle and normalized by transgenic expression of LNalpha1 chain. We suggest that LNalpha1 chain in part ameliorates the development of LNalpha2 chain deficient muscular dystrophy by retaining the binding sites for integrin alpha7Bbeta1D and alpha-dystroglycan, respectively.

Animals↗
PubMed1990

A human monoclonal autoantibody specific for human platelet glycoprotein IIb (integrin alpha IIb) heavy chain.

Splenocytes from a patient with chronic, immune-mediated thrombocytopenic purpura (ITP) were transformed with Epstein-Barr virus. A stable lymphoblastoid cell line (LCL) derived from this transformation (2A3) produces IgM antibody reactive with platelet glycoprotein IIb. 2A3 was fused to the 6-thioguanine-resistant ouabain-resistant, murine-human heteromyeloma cell line, F6. The resultant heterohybridomas were selected by growth in medium containing hypoxanthine/aminopterin/thymidine and ouabain. One hybridoma line, 2E7, produces high levels of IgM antibody (2 to 4 micrograms IgM/ml/24 hr/10(5) cells) reactive with glycoprotein IIb. 2E7 has been repeatedly subcloned by limiting dilution and has been maintained in continuous culture for 26 months. 2E7 binds to human platelets but not endothelial cells, as determined by flow cytometry, and does not react with platelets of patients with Glanzmann's thrombasthenia that lack IIb-IIIa. The epitope recognized by 2E7 is likely to be a contiguous peptide sequence since the antibody binds to the IIb heavy chain in immunoblot assays of denatured, reduced platelet protein. Treatment of intact platelets or purified IIb-IIIa with papain or chymotrypsin, but not SV8 protease, destroys the epitope. Thus, the 2E7 epitope may be at or very close to a site on IIb that is cleaved by these proteases. The expression of the 2E7 epitope is significantly affected by the presence of divalent cations. Treatment of intact platelets with EDTA at 37 degrees C results in a three-to four-fold increase in the number of 2E7 molecules bound per platelet and an eight-fold increase in the affinity of the antibody. The binding of 2E7 to normal platelets does not inhibit any of the functions attributed to IIb-IIIa, such as fibrinogen-dependent platelet aggregation or clot retraction. 2E7 represents the first human monoclonal antibody reported to recognize an epitope on platelet glycoprotein IIb. The epitope is unique to IIb and not shared by other integrin alpha subunits.

Adolescent↗
PubMed1997

Localization of laminin, fibronectin, E-cadherin, and integrins in endometrium and endometriosis.

OBJECTIVE: To compare the localization of adhesion proteins (laminin and fibronectin) and their receptors of the integrin family in endometriosis and endometrium. DESIGN: An immunohistochemical study. SETTING: University Hospital, Department of Gynecology and Department of Cell Biology. PATIENT(S): Eighteen endometriosis patients undergoing laparoscopy for pain or infertility and nine control patients undergoing laparoscopy for sterilization or hysterectomy. MAIN OUTCOME MEASURE(S): The expression of adhesion glycoproteins (laminin and fibronectin), their receptors alpha 1 beta 1, alpha 2 beta 1, alpha 3 beta 1, alpha 5 beta 1, and alpha 6 beta 1, and E-cadherin was determined by immunohistochemistry on frozen sections. RESULT(S): The distribution of both adhesive glycoproteins, laminin and fibronectin, and their receptors was identical in endometriosis and endometrium. Fibronectin receptors (alpha 4 beta 1, alpha 5 beta 1) displayed distinct expression patterns in endometrium and endometriosis. No endometrial glands showed positive staining for the alpha 5 chain, whereas this integrin subunit was detected in almost all endometriotic lesions. The integrin alpha 4 chain was present in all endometriotic glands but was absent from endometrial glands in the proliferative phase of the cycle. CONCLUSION(S): No difference in cell adhesion molecule localization nor receptors was observed between endometriotic and endometrial samples, except for fibronectin receptors. Their expression persisted around endometriotic glands but not in endometrium. These results suggest that fibronectin receptors could play a role in the persistence of endometriotic lesions, despite menstruation in corresponding eutopic endometrium.

Adult↗
PubMed1994

Comparative evaluation of integrin alpha- and beta-chain expression in colorectal carcinoma cell lines and in their tumours of origin.

The integrin family consists of broadly expressed cell surface adhesion receptors, each member of which is composed of a non-covalently linked alpha/beta heterodimer. Integrin receptors are involved in the interaction with matrix proteins and may contribute to invasion and metastasis of carcinomas. To examine the biological role integrins play in colorectal carcinoma we compared the expression of integrin alpha- and beta-subunits in situ and in vitro. Eight newly established cell lines derived from immunohistochemically characterized colorectal carcinomas together with two sublines obtained after nude mouse passage and the commonly used colon carcinoma lines HT-29, SW480, SW620, and COLO 205 were investigated by immunocytochemistry and flow cytometry. The carcinomas in situ expressed alpha 1-, alpha 2-, alpha 3-, alpha 6-, alpha v- and beta 1-subunits in variable amounts while being devoid of alpha 4, alpha 5, and beta 3. The individual integrin profile of the tumour in tissue was essentially maintained in vitro. However, a neo expression of the alpha 5 chain was found, together with an induction or increase in alpha 1, alpha 2, alpha 3, alpha v and beta 1 levels. No decrease in integrin subunit expression was observed. Standard-serum and serum-free medium revealed no striking differences in alpha- and beta-chain expression in the cell lines HT-29 and COLO 205. In serum-free medium, SW480 showed a slight increase of alpha 1 and alpha 5 and a decrease of alpha 3 and alpha v while SW620 expressed more alpha 1. We conclude that the great variability of adhesion receptor expression of the integrin family in colorectal carcinomas in situ is essentially maintained in vitro, although culture conditions which are only marginally influenced by serum factors unpredictably lead to some increase in expression or even induction of several integrin subunits.

Antibodies, Monoclonal↗
PubMed1994

Minimum alpha chain cytoplasmic tail sequence needed to support integrin-mediated adhesion.

Previously, we found that deletion of the integrin alpha 4 and alpha 2 subunit cytoplasmic domains, just after the conserved GFFKR motif, causes a loss of adhesive activity mediated by VLA-4 or VLA-2, respectively (Kassner, P.D., and Hemler, M. E. (1993) J. Exp. Med. 178, 649-60; Kawaguchi, S., and Hemler, M. E. (1993) J. Biol. Chem. 268, 16279-12685). Here, we show for alpha 4 and alpha 2 chains (expressed in MIP101 and Chinese hamster ovary cells) that adding only 3-4 amino acids after the GFFKR motif restores substantial adhesive activity and that 5-7 amino acids confers maximal adhesive activity (to VCAM-1, CS1 peptide, or collagen, respectively). Point mutations within the most critical 5 alpha 4 residues had no effect on alpha 4 adhesive activity, nor did exchange of the alpha 4 tail with that of alpha 2. Thus, only a short and relatively nonspecific stretch of alpha chain cytoplasmic domain amino acids may be required to achieve maximal integrin adhesive activity. Also, comprehensive divalent cation titration assays revealed (i) that deletion of alpha chain cytoplasmic domains caused a marked decrease in the efficiency of divalent cation utilization during cell adhesion assays and (ii) that cytoplasmic domain deletion effects could be either suppressed or accentuated depending on the type and amount of divalent cation and the cellular environment utilized. Notably, integrin alpha chain tail deletions did not appear to alter the intrinsic ability to interact with ligand because deletion effects were minimal in the presence of metabolic energy inhibitors and were absent during cell-free ligand binding assays.

Amino Acid Sequence↗