Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Tetraspanin 29”

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 19 recordsLinked to original sources
PubMed1998

Transmembrane 4 superfamily as a prognostic factor in pancreatic cancer.

Several members of the transmembrane 4 superfamily (TM4SF) have been reported to be related to tumor progression and metastasis. The aims of our study were to clarify the relationship between TM4SF and pancreatic cancer and to determine the prognostic significance of TM4SF in human pancreatic cancer. The mRNA levels for MRP-1/CD9, KAI1/CD82 and ME491/CD63, which belong to the TM4SF gene family, were evaluated in 40 resectable pancreatic adenocarcinomas using reverse transcriptase-PCR. MRP-1/CD9 gene expression was associated with lymph node status, and with pathological status. Moreover, MRP-1/CD9 expression was inversely associated with histo-pathological grading. KAI1/CD82 gene expression was inversely associated with tumor status. ME491/CD63 gene expression, however, was conserved in all pancreatic cancers. The overall survival rate for the 22 patients whose tumors had decreased MRP-1/CD9 gene expression was strikingly lower than that for the 18 patients with MRP-1/CD9-positive tumors. The overall survival rate of the 15 patients who were KAI1/CD82-positive was significantly higher than that of the 25 patients with decreased KAI1/CD82 gene expression. In a multivariate analysis using the Cox proportional hazards model, MRP-1/CD9 and KAI1/CD82 status was found to be the most significant.

Adenocarcinoma↗
PubMed1996

CD9, CD63, CD81, and CD82 are components of a surface tetraspan network connected to HLA-DR and VLA integrins.

CD9, CD63, CD81, and CD82 are glycoproteins of unknown function which belong to the tetraspan superfamily. These molecules have short cytoplasmic sequences, four transmembrane domains and two unequal extracellular regions. Here, we show that these molecules are associated with each other on cell surface and with other glycoproteins such as very late antigen (VLA) integrins and HLA-DR antigens. Moreover, the VLA integrins and HLA-DR antigens were also found to be associated. The interactions of these molecules were analyzed by transfection experiments. It is demonstrated that overexpression of CD9 antigen in Raji cells leads to a lower efficiency of precipitation of CD81 and CD82, suggesting a direct interaction between these molecules. In these cells, the co-precipitation of CD81 and CD82 was not modified, suggesting that these tetraspans did not compete for association. However, in COS-7 cells, transfection of both CD81 and CD82 led to a marked reduction of the number of CD9/CD81 or CD9/CD82 complexes compared to single-transfected cells, and this was associated with the appearance of CD81/CD82 complexes. Therefore, in this cellular system, CD9 competes with CD81 and CD82 for association with the other tetraspan proteins. Finally, the tetraspans do not compete for the association with integrins or HLA-DR. Indeed, when CD9 was expressed in Raji cells, it was incorporated into the pre-existing complexes of these molecules with CD81 and CD82. These data suggest the existence of a tetraspan network which, by connecting several molecules, may organize the positioning of cell surface proteins and play a role in signal transduction, cell adhesion, and motility.

Animals↗
PubMed2002

The tetraspanin protein, CD9, is expressed by progenitor cells committed to oligodendrogenesis and is linked to beta1 integrin, CD81, and Tspan-2.

Previous studies identified the tetraspanin protein CD9 in myelinating oligodendrocytes. The present report extends these observations by identifying CD9 in a subpopulation of oligodendrocyte progenitor cells (OPCs) and in premyelinating oligodendrocytes in rodents. NG2-positive cells expressed CD9 in a temporal and spatial pattern during development that was consistent with CD9 expression in OPCs just prior to their differentiation into premyelinating oligodendrocytes. NG2-positive cells in mature brains were CD9-negative. CD9 expression during oligodendrocyte development in vitro supported this hypothesis, as all CD9-positive cells became O4-positive when switched to oligodendrocyte differentiating media. CD9 immunoreactivity was enriched in myelinating oligodendrocytes and their processes, and the outer aspects of myelin internodes. Immunoprecipitation of CD9 from postnatal rat cerebrum coprecipitated beta1 integrin, CD81, and Tspan-2, another tetraspanin protein recently identified in oligodendrocytes. Following surface biotinylation of oligodendrocytes in vitro, biotinylated beta1 integrin was identified in a CD9 immunoprecipitate. These data support a molecular link between surface integrins and a CD9, Tspan-2 molecular web during the differentiation of oligodendrocytes. Oligodendrocyte production and myelination appears to be normal in CD9-deficient mice. These data support the hypothesis that CD9 helps form the tetraspanin web beneath the plasma membranes of progenitor cells committed to oligodendrogenesis, but that CD9 is not essential for oligodendrogenesis and myelination.

Animals↗
PubMed1993

Expression of the neuroglandular antigen and analogues in melanoma. CD9 expression appears inversely related to metastatic potential of melanoma.

Immunohistological methods were used to examine the relation between the metastatic potential of melanoma and expression of the neuroglandular antigen (CD63) and other members of this family of molecules, CD53, CD37, CD9 and the target of an anti-proliferative antibody (TAPA-I), as well as MHC-class-I and -II antigens. The criteria used to establish metastatic potential were their relation to thickness of the primary melanoma, and differences in expression between vertical and radial growth phases of primary melanoma and between primary and metastatic melanoma. Studies on basal-cell carcinoma (BCC) and squamous-cell carcinoma (SCC) were also included as controls for malignant skin cancers with low metastatic potential. Expression of CD9 and MHC-class-I antigen was found to be inversely related to thickness of the primary tumor, and CD9 was expressed predominantly on primary rather than on metastatic tumors. CD9 expression correlated with MHC-class-I expression on melanoma, and both were expressed on BCCs and SCCs having low metastatic potential, but not on compound nevi. CD63 and TAPA-I were expressed on nevi but not on SCC and BCC. Leu 13 is a molecule associated with TAPA-I in lymphomas, and was found to be expressed in sections from 5 out of 34 primary and 5 out of 21 metastatic melanoma. CD53 and CD37 were not detected on melanoma. Our results indicate that several members of the neuroglandular antigen are expressed in melanoma and that low expression of CD9 on primary melanomas might have prognostic significance with respect to the potential for metastasis.

Antigens, CD↗
PubMed1996

CD63 associates with transmembrane 4 superfamily members, CD9 and CD81, and with beta 1 integrins in human melanoma.

CD63 belongs to the Transmembrane 4 superfamily (TM4SF) of membrane proteins whose functions are largely unknown. Previous results have suggested that CD63 may play an important role in the regulation of melanoma progression. To explore the role of CD63 in melanoma we have examined its association with other molecules by immunoprecipitation of CD63 from detergent induced lysates of melanoma cells. These results are the first to demonstrate an association between CD63 and two other TM4SF members, CD9 and CD81 in 2 human melanoma cell lines. We are also able to identify an association between CD9 and CD63 with beta 1 integrins in melanoma. The results suggest that CD63 is capable of forming multicomponent complexes with TM4SF members and beta 1 integrins on the surface of melanoma. These findings provide further insights into the function of CD63.

Aged↗
PubMed1995

Genomic structure of SAS, a member of the transmembrane 4 superfamily amplified in human sarcomas.

SAS is a recently identified member of the transmembrane 4 superfamily (TM4SF) that is frequently amplified in human sarcomas. To further its characterization and to confirm its classification, the genomic structure of the SAS gene was determined. The SAS gene covers approximately 3.2 kb of DNA. It contains six exons within its translated region, three of which are highly conserved in the TM4SF. 5' to the translation start site are two putative transcription start sites, two CCAAT consensus sequences, and potential binding sites for both Sp1 and ATF transcription factors. Comparison of SAS organization to human ME491, CD9, and CD53 and murine CD53 and TAPA-1 confirms that SAS is a member of this family of genes and is consistent with the theory that these genes arose through duplication and divergent evolution.

Amino Acid Sequence↗
PubMed1999

Tetraspanins expressed in the embryonic chick nervous system.

Proteins of the tetraspanin superfamily participate in the formation of plasma membrane signaling complexes; recent evidence implicates neuronal tetraspanins in axon growth and target recognition. We used a degenerate PCR screen to identify cDNAs encoding tetraspanins expressed in the embryonic spinal cord. Two cDNAs identified apparently represent chick homologues of NAG-2 (cnag) and CD9 (chCD9). A third clone encodes a novel tetraspanin (neurospanin). All three mRNAs are widely expressed but exhibit developmentally distinct patterns of expression in the nervous system. Both neurospanin and cnag exhibit high relative expression in nervous tissue, including brain, spinal cord and dorsal root ganglia (DRG).

Amino Acid Sequence↗
PubMed1999

A general approach to the generation of monoclonal antibodies against members of the tetraspanin superfamily using recombinant GST fusion proteins.

Tetraspanins belong to a rapidly growing family of proteins characterized by the presence of four conserved transmembrane segments and are involved in such diverse functions as cellular activation, adhesion, migration and differentiation. In an effort to develop reagents against newly discovered tetraspanins, we have devised a simple method for the screening of monoclonal antibodies (mAbs) using recombinant GST fusion proteins. GST fusion proteins containing the second extracellular domain of different tetraspanins (CD9, CD63, CD53, CD81, A15 or CO-029) were produced separately. Mice were immunized with cells having a high expression of the chosen tetraspanin and the constructs were used to screen hybridomas in a solid phase ELISA. Several clones binding the fusion protein were identified for each construct tested: four anti-CD9 hybridoma clones, four anti-CD63, two anti-CD53, two anti-CD81, three anti-A15 and one anti-CO-029. All the newly developed mAbs recognized the native proteins by flow cytometry, immunofluorescence staining of cells and immunoprecipitation and bound to the denatured proteins on immunoblotting. Use of GST fusion protein constructs in a simple ELISA can facilitate screening for mAbs to members of the tetraspanin family, especially in cases where information is limited to the nucleotide sequence. The mAbs obtained by this strategy should prove to be valuable tools for functional studies of newly discovered tetraspanins.

Animals↗
PubMed2002

Expression of transmembrane 4 superfamily (TM4SF) proteins and their role in hepatic stellate cell motility and wound healing migration.

BACKGROUND/AIMS: Migration of activated hepatic stellate cells (HSC) is a key event in the progression of liver fibrosis. Little is known about transmembrane proteins involved in HSC motility. Tetraspanins (TM4SF) have been implicated in cell development, differentiation, motility and tumor cell invasion. We evaluated the expression and function of four TM4SF, namely CD9, CD81, CD63 and CD151, and their involvement in HSC migration, adhesion, and proliferation. METHODS/RESULTS: All TM4SF investigated were highly expressed at the human HSC surface with different patterns of intracellular distribution. Monoclonal antibodies directed against the four TM4SF inhibited HSC migration induced by extracellular matrix proteins in both wound healing and haptotaxis assays. This inhibition was independent of the ECM substrates employed (collagen type I or IV, laminin), and was comparable to that obtained by incubating the cells with an anti-beta1 blocking mAb. Importantly, cell adhesion was unaffected by the incubation with the same antibodies. Co-immunoprecipitation studies revealed different patterns of association between the four TM4SF studied and beta1 integrin. Finally, anti-TM4SF antibodies did not affect HSC growth. CONCLUSIONS: These findings provide the first characterization of tetraspanins expression and of their role in HSC migration, a key event in liver tissue wound healing and fibrogenesis.

Antibodies, Monoclonal↗
PubMed2005

The tetraspanin D6.1A and its molecular partners on rat carcinoma cells.

Tetraspanins function as molecular organizers of multi-protein complexes by assembling primary complexes of a relatively low mass into extensive networks involved in cellular signalling. In this paper, we summarize our studies performed on the tetraspanin D6.1A/CO-029/TM4SF3 expressed by rat carcinoma cells. Primary complexes of D6.1A are almost indistinguishable from complexes isolated with anti-CD9 antibody. Indeed, both tetraspanins directly associate with each other and with a third tetraspanin, CD81. Moreover, FPRP (prostaglandin F2alpha receptor-regulatory protein)/EWI-F/CD9P-1), an Ig superfamily member that has been described to interact with CD9 and CD81, is also a prominent element in D6.1A complexes. Primary complexes isolated with D6.1A-specific antibody are clearly different from complexes containing the tetraspanin CD151. CD151 is found to interact only with D6.1A if milder conditions, i.e. lysis with LubrolWX instead of Brij96, are applied to disrupt cellular membranes. CD151 probably mediates the interaction of D6.1A primary complexes with alpha3beta1 integrin. In addition, two other molecules were identified to be part of D6.1A complexes at this higher level of association: type II phosphatidylinositol 4-kinase and EpCAM, an epithelial marker protein overexpressed by many carcinomas. The characterization of the D6.1A core complex and additional more indirect interactions will help to elucidate the role in tumour progression and metastasis attributed to D6.1A.

Animals↗
PubMed1998

Pattern of expression of tetraspanin antigen genes in Burkitt lymphoma cell lines.

Tetraspanin antigens are implicated in the prognosis of different types of tumours. In this study we determine by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) the level of 13 tetraspan messages in 21 Burkitt lymphoma (BL) cell lines. All tumour cell lines have a common pattern of tetraspanin gene expression. There are five antigens which are detected in 90% of cell lines at high levels, CD53, CD81, CD63, SAS and CD82. Another two, CD9 and CD37, were detected in 60% of cell lines, and have a very variable level of expression. The remaining antigens, A15, CoO29, KRAG, L6, TI-1 and il-TMP, are expressed at low levels in very few cell lines without any specific pattern. The level of gene expression corresponds with the level of cell surface antigen determined by flow cytometry. The average number of tetraspan proteins expressed per cell line is six. These proteins may form subunits of an oligomeric structure with 24 transmembrane domains. There are no major differences in tetraspan expression pattern among sporadic or endemic tumours, type of translocation or Epstein-Barr virus status, suggesting the original cell of these tumours is the same, probably a late pre-B cell, at the CD9 to CD37 transition point. Tetraspanin gene expression is consistent with BL being a single entity, despite variations in other parameters.

Antigens, CD↗
PubMed2000

Tetraspanins are localized at motility-related structures and involved in normal human keratinocyte wound healing migration.

We have described previously that beta1 integrins, which mediate keratinocyte cell adhesion and migration, are in ligand-occupied conformation at the basal surface but not at the lateral and apical surfaces of keratinocytes. This led us to study the cellular localization and function of tetraspanin molecules, which have been postulated to modulate integrin activity. We found that CD9 and CD81 are highly expressed by keratinocytes clearly delineating filopodia at lateral and apical surfaces. CD63 and CD151 are largely expressed in the intracellular compartment, although some membrane expression is observed. We found accumulation of CD9, CD81, and CD151 together with alpha3 and beta1 integrins at intercellular junctions. In low calcium medium, this intercellular space is crossed by a zipper of filopodia enriched in alpha3beta1 and tetraspanin proteins. Interestingly, the expression of CD9, CD81, and beta1 and alpha3 integrins was detected in the footprints and rippings of motile keratinocytes, suggesting their role in both adhesion to extracellular matrix and keratinocyte motility. beta1 integrins were only partially activated in the rips, whereas cytoskeleton-linking proteins such as talin were completely absent. On the other hand, antitetraspanin antibodies did not stain focal adhesions, which contain talin. The involvement of tetraspanins in keratinocyte motility was assessed in a wound healing migration assay. Inhibition of cell migration was observed with antibodies to CD9, CD81, beta1, and alpha3, and, to a lesser extent, to CD151. Together these results indicate that tetraspanin-integrin complexes might be involved in transient adhesion and integrin recycling during keratinocyte migration, as well as in intercellular recognition.

Antigens, CD↗
PubMed1997

NAG-2, a novel transmembrane-4 superfamily (TM4SF) protein that complexes with integrins and other TM4SF proteins.

Transmembrane-4 superfamily (TM4SF) proteins form complexes with integrins and other cell-surface proteins. To further characterize the major proteins present in a typical TM4SF protein complex, we raised monoclonal antibodies against proteins co-immunoprecipitated with CD81 from MDA-MB-435 breast cancer cells. Only two types of cell-surface proteins were recognized by our 35 selected antibodies. These included an integrin (alpha6beta1) and three different TM4SF proteins (CD9, CD63, and NAG-2). The protein NAG-2 (novel antigen-2) is a previously unknown 30-kDa cell-surface protein. Using an expression cloning protocol, cDNA encoding NAG-2 was isolated. When aligned with other TM4SF proteins, the deduced amino acid sequence of NAG-2 showed most identity (34%) to CD53. Flow cytometry, Northern blotting, and immunohistochemistry showed that NAG-2 is widely present in multiple tissues and cell types but is absent from brain, lymphoid cells, and platelets. Within various tissues, strongest staining was seen on fibroblasts, endothelial cells, follicular dendritic cells, and mesothelial cells. In nonstringent detergent, NAG-2 protein was co-immunoprecipitated with other TM4SF members (CD9 and CD81) and integrins (alpha3beta1 and alpha6beta1). Also, two-color immunofluorescence showed that NAG-2 was co-localized with CD81 on the surface of spread HT1080 cells. These results confirm the presence of NAG-2 in specific TM4SF.TM4SF and TM4SF-integrin complexes.

Amino Acid Sequence↗
PubMed2000

Evaluation of prototype transmembrane 4 superfamily protein complexes and their relation to lipid rafts.

Recent literature suggests that tetraspanin proteins (transmembrane 4 superfamily; TM4SF proteins) may associate with each other and with many other transmembrane proteins to form large complexes that sometimes may be found in lipid rafts. Here we show that prototype complexes of CD9 or CD81 (TM4SF proteins) with alpha(3)beta(1) (an integrin) and complexes of CD63 (a TM4SF protein) with phosphatidylinositol 4-kinase (PtdIns 4-K) may indeed localize within lipid raft-like microdomains, as seen by three different criteria. First, these complexes localize to low density light membrane fractions in sucrose gradients. Second, CD9 and alpha(3) integrin colocalized with ganglioside GM1 as seen by double staining of fixed cells. Third, CD9-alpha3beta1 and CD81-alpha3beta1 complexes were shifted to a higher density upon cholesterol depletion from intact cells or cell lysate. However, CD9-alpha3beta1, CD81-alpha3beta1, and CD63-PtdIns 4-K complex formation itself was not dependent on localization into raftlike lipid microdomains. These complexes did not require cholesterol for stabilization, were maintained within well solubilized dense fractions from sucrose gradients, were stable at 37 degrees C, and were small enough to be included within CL6B gel filtration columns. In summary, prototype TM4SF protein complexes (CD9-alpha3beta1, CD81-alpha3beta1, and CD63-PtdIns 4-K) can be solubilized as discrete units, independent of lipid microdomains, although they do associate with microdomains resembling lipid rafts.

Antigens, CD↗
PubMed2000

Importance of the major extracellular domain of CD9 and the epidermal growth factor (EGF)-like domain of heparin-binding EGF-like growth factor for up-regulation of binding and activity.

Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is a member of the EGF family of growth factors. The membrane-anchored form of HB-EGF (proHB-EGF) is mitogenically active to neighboring cells as well as being a precursor of the soluble form. In addition to its mitogenic activity, proHB-EGF has the property of binding to diphtheria toxin (DT), serving as the specific receptor for DT. Tetramembrane-spanning protein CD9, a member of the TM4 superfamily, is physically associated with proHB-EGF at the cell surface and up-regulates both mitogenic and DT binding activities of proHB-EGF. To understand this up-regulation mechanism, we studied essential regions of both CD9 and proHB-EGF for up-regulation. Immunoprecipitation experiments revealed that not only CD9 but also other TM4 proteins including CD63, CD81, and CD82 associate with proHB-EGF on the cell surface. However, these TM4 proteins did not up-regulate DT binding activity of proHB-EGF. Transfection of a series of chimeric constructs comprising CD9 and CD81 showed that the major extracellular domain of CD9 is essential for up-regulation. Assays of DT binding activity and juxtacrine mitogenic activity of the deletion mutants of proHB-EGF and chimeric molecules, derived from proHB-EGF and TGF-alpha, showed that the essential domain of proHB-EGF for up-regulation is the EGF-like domain. These results indicate that the interaction of the extracellular domains of both molecules is important for up-regulation.

Animals↗
PubMed2006

Profiling of the tetraspanin web of human colon cancer cells.

Tetraspanins are integral membrane proteins involved in a variety of physiological and pathological processes. In cancer, clinical and experimental studies have reported a link between tetraspanin expression levels and metastasis. Tetraspanins play a role as organizers of multimolecular complexes in the plasma membrane. Indeed each tetraspanin associates specifically with one or a few other membrane proteins forming primary complexes. Thus, tetraspanin-tetraspanin associations lead to a molecular network of interactions, the "tetraspanin web." We performed a proteomic characterization of the tetraspanin web using a model of human colon cancer consisting of three cell lines derived from the primary tumor and two metastases (hepatic and peritoneal) from the same patient. The tetraspanin complexes were isolated after immunoaffinity purification using monoclonal antibodies directed against the tetraspanin CD9, and the associated proteins were separated by SDS-PAGE and identified by mass spectrometry using LC-MS/MS. This allowed the identification of 32 proteins including adhesion molecules (integrins, proteins with Ig domains, CD44, and epithelial cell adhesion molecule) (EpCAM), membrane proteases (ADAM10, TADG-15, and CD26/dipeptidyl peptidase IV), and signaling proteins (heterotrimeric G proteins). Importantly some components were differentially detected in the tetraspanin web of the three cell lines: the laminin receptor Lutheran/B-cell adhesion molecule (Lu/B-CAM) was expressed only on the primary tumor cells, whereas CD26/dipeptidyl peptidase IV and tetraspanin Co-029 were observed only on metastatic cells. Concerning Co-029, immunohistofluorescence showed a high expression of Co-029 on epithelial cells in normal colon and a lower expression in tumors, whereas heterogeneity in terms of expression level was observed on metastasis. Finally we demonstrated that epithelial cell adhesion molecule and CD9 form a new primary complex in the tetraspanin web.

Antigens, CD↗
PubMed2006

Mapping of tetraspanin-enriched microdomains that can function as gateways for HIV-1.

Specific spatial arrangements of proteins and lipids are central to the coordination of many biological processes. Tetraspanins have been proposed to laterally organize cellular membranes via specific associations with each other and with distinct integrins. Here, we reveal the presence of tetraspanin-enriched microdomains (TEMs) containing the tetraspanins CD9, CD63, CD81, and CD82 at the plasma membrane. Fluorescence and immunoelectron microscopic analyses document that the surface of HeLa cells is covered by several hundred TEMs, each extending over a few hundred nanometers and containing predominantly two or more tetraspanins. Further, we reveal that the human immunodeficiency virus type 1 (HIV-1) Gag protein, which directs viral assembly and release, accumulates at surface TEMs together with the HIV-1 envelope glycoprotein. TSG101 and VPS28, components of the mammalian ESCRT1 (endosomal sorting complex required for transport), which is part of the cellular extravesiculation machinery critical for HIV-1 budding, are also recruited to cell surface TEMs upon virus expression, suggesting that HIV-1 egress can be gated through these newly mapped microdomains.

Antigens, CD↗