Biomedical subjects

R Chiquet-Ehrismann

Publications and source records attributed to R Chiquet-Ehrismann.

89 records · Page 5Linked to original sources

PubMed1990

Tenascin expression in the human endometrium and in endometrial adenocarcinomas.

To investigate the involvement of tenascin, an extracellular matrix glycoprotein, in epithelial growth and malignancy, its specific distribution pattern in the human uterus was examined immunohistochemically. During the proliferative phase of the menstrual cycle, this antigen was found as a sharp band around the endometrial glands. The immunoreactivity persisted until the early postovulatory phase of the menstrual cycle, but was not detectable in the glandular or stromal compartment during this later secretory stage, instead endometrial arterioles were immunostained. In marked contradistinction, when antibodies directed against tenascin were applied to sections of endometrial adenocarcinoma, almost the entire extracellular space stained, whereas the neoplastic cells themselves were nonreactive, whatever the degree of tumor differentiation. In precancerous proliferative lesions of the endometrium, tenascin's presence was variable. It was detectable around some superficial glands demonstrating cystic hyperplasia and around all deeply situated glands at the endometrial/myometrial interface. In cases of adenomatous hyperplasia, tenascin immunolocalized throughout the extracellular space of the stroma and the staining intensity was increased as the hyperplasia became more atypical. We therefore conclude that tenascin may be a stromal marker for epithelial proliferative states including those associated with malignancies of the endometrium.

Adenocarcinoma↗

PubMed1989

Two contrary functions of tenascin: dissection of the active sites by recombinant tenascin fragments.

A structural and functional model of tenascin was elaborated using recombinant parts of three alternatively spliced tenascin variants and anti-tenascin monoclonal antibodies. The fusion proteins were compared with intact tenascin for their functions and by electron microscopy. A strong cell binding site was localized within 104 amino acids. This fragment also contains the epitope of the monoclonal antibody anti-Tn68, which inhibits cell attachment to tenascin and binds near the tips of the six arms of tenascin. In contrast, constructs containing the 13 1/2 EGF-like repeats of tenascin showed an antiadhesive effect. The coexistence of the two contrary signals on the same molecule might be responsible for the versatile features of tenascin.

Amino Acid Sequence↗

PubMed1989

Participation of tenascin and transforming growth factor-beta in reciprocal epithelial-mesenchymal interactions of MCF7 cells and fibroblasts.

The tumor stroma is essential for the development of the tumor epithelium. Tenascin is an extracellular matrix protein highly expressed in the stroma of malignant mammary tumors. We therefore tested whether in vitro MCF7 cells were able to induce fibroblasts to synthesize tenascin. Indeed MCF7 cell-conditioned medium contained tenascin-inducing activity. This activity was shown to be transforming growth factor-beta. The morphology of the MCF7 cells was in turn affected by the addition of tenascin to the culture medium. The cells partially detached from the substratum and lost their cell-cell contracts.

Animals↗

PubMed1989

The effect of tenascin and embryonic basal lamina on the behavior and morphology of neural crest cells in vitro.

We have investigated the morphology and migratory behavior of quail neural crest cells on isolated embryonic basal laminae or substrata coated with fibronectin or tenascin. Each of these substrata have been implicated in directing neural crest cell migration in situ. We also observed the altered behavior of cells in response to the addition of tenascin to the culture medium independent of its effect as a migratory substratum. On tenascin-coated substrata, the rate of neural crest cell migration from neural tube explants was significantly greater than on uncoated tissue culture plastic, on fibronectin-coated plastic, or on basal lamina isolated from embryonic chick retinae. Neural crest cells on tenascin were rounded and lacked lamellipodia, in contrast to the flattened cells seen on basal lamina and fibronectin-coated plastic. In contrast, when tenascin was added to the culture medium of neural crest cells migrating on isolated basal lamina, a significant reduction in the rate of cell migration was observed. To study the nature of this effect, we used human melanoma cells, which have a number of characteristics in common with quail neural crest cells though they would be expected to have a distinct family of integrin receptors. A dose-dependent reduction in the rate of translocation was observed when tenascin was added to the culture medium of the human melanoma cell line plated on isolated basal laminae, indicating that the inhibitory effect of tenascin bound to the quail neural crest surface is probably not solely the result of competitive inhibition by tenascin for the integrin receptor. Our results show that tenascin can be used as a migratory substratum by avian neural crest cells and that tenascin as a substratum can stimulate neural crest cell migration, probably by permitting rapid detachment. Tenascin in the medium, on the other hand, inhibits both the migration rates and spreading of motile cells on basal lamina because it binds only the cell surface and not the underlying basal lamina. Cell surface-bound tenascin may decrease cell-substratum interactions and thus weaken the tractional forces generated by migrating cells. This is in contrast to the action of fibronectin, which when added to the medium stimulates cell migration by binding both to neural crest cells and the basal lamina, thus providing a bridge between the motile cells and the substratum.

Animals↗

PubMed1989

Tenascin, an extracellular matrix protein, exerts immunomodulatory activities.

Tenascin is a nonubiquitous extracellular matrix protein mainly expressed during morphogenesis in embryonal life. In adults it reappears in malignant tumors and during inflammation and tissue repair. Extracellular matrix proteins can alter cell morphology, adhesion, motility, differentiation, and growth. Since cells of the immune system can express receptors for extracellular matrix, we investigated the effects of tenascin on human monocytes and T and B lymphocytes. Tenascin inhibited monocyte adhesion to fibronectin and enhanced the LFA-1 (lymphocyte function-associated antigen 1)-dependent clustering of Epstein-Barr virus-transformed B cells. The physiological consequences of the effects of tenascin were studied in several T-cell activation models. Tenascin inhibited T-cell activation induced by a soluble antigen (tetanus toxoid), alloantigens, or the mitogen concanavalin A. However, T-cell activation with phytohemagglutinin, crosslinked anti-CD3 antibody, or a mixture of ionomycin and phorbol ester was not inhibited by tenascin. Tenascin did not prevent interleukin 2-dependent T-cell growth or the cytolytic activity of an antigen-specific CD4+ T-cell clone. These results suggest that tenascin alters the adhesion properties of human monocytes, B cells, and T cells. The in vitro immunosuppressive activity of tenascin might be due to abrogation of an accessory cell function at an early stage of the interaction between antigen-presenting cells and T cells.

Adjuvants, Immunologic↗

PubMed1988

Tenascin interferes with fibronectin action.

Primary chick embryo fibroblasts attach to a tenascin substrate, but remain rounded and do not spread out. The proportion between tenascin and fibronectin in mixtures used to coat the substrate determines the shape of the cells. Tenascin inhibits integrin-mediated chick fibroblast attachment to fibronectin, laminin, and the GRGDS peptide. Rat fibroblast attachment to fibronectin, but not to laminin, is inhibited by tenascin. A monoclonal antibody against tenascin, as well as its Fab fragments, is able to neutralize the inhibitory activity on cell attachment and is therefore assumed to mask the cell-binding site of tenascin. On electron micrographs showing this monoclonal antibody bound to tenascin, its epitope can be localized to the terminal knob at the distal ends of the tenascin arms.

Animals↗

PubMed1988

Tenascin: cDNA cloning and induction by TGF-beta.

cDNA clones coding for tenascin, an extracellular matrix glycoprotein with a restricted tissue distribution, were isolated from a chicken fibroblast cDNA expression library using a specific tenascin antiserum. Antibodies eluted from the cDNA-encoded fusion proteins reacted exclusively with tenascin. Limited trypsin treatment of purified tenascin resulted in a peptide which confirmed the deduced protein sequences. The largest clone encoding 632 amino acids showed a cysteine-rich region containing 13 consecutive epidermal growth factor-like repeats of unusual uniformity. Northern blot analysis revealed 8- to 9-kb messages. Tenascin is shown to be induced in vitro by fetal calf serum as well as by transforming growth factor beta (TGF-beta). A 4-fold increase in tenascin secretion by chick embryo fibroblasts was seen after TGF-beta treatment. The induction of tenascin protein synthesis was preceded by an increase of tenascin mRNA as determined by Northern blot analysis. The induction of tenascin was compared with fibronectin. The accumulation of the two extracellular matrix proteins in the medium was differentially affected by fetal calf serum and TGF-beta and the increase was in both cases higher for tenascin.

Amino Acid Sequence↗

PubMed1988

Immunohistochemical localization of the matrix glycoprotein tenascin in the skull of the growing rat.

Tenascin is an extracellular matrix glycoprotein which interacts with other matrix molecules and with cells, and which appears to play important roles in growth and differentiation. The immunohistochemistry of sections of newborn, 5-day and 20-day-old rats showed that accumulation of tenascin was largely restricted to bones, cartilages and teeth. It was also present in the periosteal and endosteal surfaces of membrane bones, in perichondrium, and ion the dental pulp, but was absent from mature bone, cartilage and dentine. In nasal cartilage, tenascin was present only in the perichondrium, whereas in the condylar cartilage staining was observed in the proliferating and maturing cell layers but not in the hypertrophied cartilage. These differences may reflect differences in the growth mechanisms of primary and secondary cartilages. Accumulation of tenascin was particularly striking in areas where the periosteum or perichondrium was thickened such as sites of some muscle attachments, sutures and condylar cartilage. The restricted distribution of tenascin is unlike the patterns observed for other extracellular matrix molecules. Tenascin may have a unique role in bone growth and remodelling in the craniofacial region.

Animals↗

PubMed1988

Epithelial induction of stromal tenascin in the mouse mammary gland: from embryogenesis to carcinogenesis.

The distribution of the extracellular matrix glycoprotein tenascin was studied by immunofluorescence in the developmental history of the mouse mammary gland from embryogenesis to carcinogenesis. Tenascin appeared only in the mesenchyme immediately surrounding the epithelia just starting morphogenesis, that is, in embryonic mammary glands from 13th to 16th day of gestation, in mammary endbuds which are a characteristic structure starting development during maturation of the mammary gland, and in the stroma of malignant mammary tumors. However, tenascin was absent in the elongating ducts of embryonic, adult, proliferating, and involuting mammary glands and preneoplastic hyperplastic alveolar nodules. The transplantation of embryonic submandibular mesenchyme into adult mammary glands induces the development of duct-alveolus nodules, which morphologically resemble developing endbuds. Tenascin reappeared around those nodules during the initial stages of their development. Tenascin expression could be induced experimentally in several ways. First, tenascin was detected at the site where the first mammary tumor cells GMT-L metastasized. Second, tenascin was detected in the connective tissue in the tumors derived from the injected C3H mammary tumor cell line CMT315 into Balb/c nude mouse. Cross-strain marker anti-CSA antiserum clearly showed that the tenascin-positive fibroblasts were of Balb/c origin. Third, when embryonic mammary epithelium was explanted on to embryonic mammary fat pad cultures, the mesenchymal cells condensed immediately surrounding the epithelium. Tenascin was detected in these condensed cells. From these three observations we conclude that both embryonic and neoplastic epithelium induced tenascin synthesis in their surrounding mesenchyme.

Animals↗

PubMed1988

The high-molecular-weight J1 glycoproteins are immunochemically related to tenascin.

The J1 glycoproteins have been shown to mediate neuron-astrocyte adhesion and appear in the nervous system as four species of Mr 160,000 (J1-160), 180,000 (J1-180), 200,000 (J1-200), and 220,000 (J1-220), respectively. Tenascin is a disulfide-linked oligomeric, extracellular matrix glycoprotein of subunit Mr 170,000, 190,000, 200,000, and 220,000, which has been proposed to promote epithelial cell proliferation. In view of the structural similarities of the molecules we have used immunohistochemical and immunochemical techniques to compare them. Immunohistochemically, polyclonal J1 and tenascin antibodies yielded identical staining patterns in non-nervous-system tissues, and staining could be completely blocked by preincubating the sera with purified tenascin. In the central nervous system all structures expressing tenascin immunoreactivity were also recognized by J1 antibodies. However, not all J1-positive structures were also tenascin-positive, indicating that J1 antibodies recognized additional epitopes not present on tenascin. Western-blot experiments performed with affinity-purified polyclonal J1 antibodies showed that J1 glycoproteins can be subdivided into two separate pairs, J1-160/180 and J1-200/220, which share a small degree of homology. Western-blot experiments and sequential immunoprecipitations on biosynthetically [35S]methionine- or 125I-radiolabeled J1 glycoproteins carried out with polyclonal J1 and tenascin antibodies demonstrated that J1-200/220 is immunochemically indistinguishable from tenascin. These observations suggest that one set of extracellular glycoproteins is associated with processes as different as neural histogenesis and carcinogenesis of mammary glands.

Animals↗

PubMed1988

The distribution of tenascin coincides with pathways of neural crest cell migration.

The distribution of the extracellular matrix (ECM) glycoprotein, tenascin, has been compared with that of fibronectin in neural crest migration pathways of Xenopus laevis, quail and rat embryos. In all species studied, the distribution of tenascin, examined by immunohistochemistry, was more closely correlated with pathways of migration than that of fibronectin, which is known to be important for neural crest migration. In Xenopus laevis embryos, anti-tenascin stained the dorsal fin matrix and ECM along the ventral route of migration, but not the ECM found laterally between the ectoderma and somites where neural crest cells do not migrate. In quail embryos, the appearance of tenascin in neural crest pathways was well correlated with the anterior-to-posterior wave of migration. The distribution of tenascin within somites was compared with that of the neural crest marker, HNK-1, in quail embryos. In the dorsal halves of quail somites which contained migrating neural crest cells, the predominant tenascin staining was in the anterior halves of the somites, codistributed with the migrating cells. In rat embryos, tenascin was detectable in the somites only in the anterior halves. Tenascin was not detectable in the matrix of cultured quail neural crest cells, but was in the matrix surrounding somite and notochord cells in vitro. Neural crest cells cultured on a substratum of tenascin did not spread and were rounded. We propose that tenascin is an important factor controlling neural crest morphogenesis, perhaps by modifying the interaction of neural crest cells with fibronectin.

Animals↗

PubMed1988

Immunocytochemical localisation of tenascin during the development of scleral papillae and scleral ossicles in the embryonic chick.

We have used a polyclonal antibody against tenascin (a 240 kDa extracellular matrix glycoprotein) and indirect immunofluorescence to investigate the distribution of tenascin in cryostat sections of the chick sclera during the six stages of scleral papilla development (Murray, 1943) and formation of membrane bone anlagen (mesenchymal condensations between 6-12 days of incubation - HH Stage 29-37). At Stages 1 and 2, when the papilla was a slight thickening in the conjunctival epithelium and mesenchymal condensation formation was initiated, tenascin was sparse in the sclera. At Stage 3, when the papilla had an epithelial mass intruding into the mesenchyme, there was an accumulation of tenascin fibrils along the subsurface of the papilla with fibrils extending from this region into the mesenchymal condensation. Interestingly, tenascin was sparse between papillae and between mesenchymal condensations. The Stage 4 papilla had a similar localisation of tenascin fibrils and in addition fine arborizing fibrils of tenascin were observed within the basal epithelia of the papilla adjacent to the epithelial-mesenchymal interface (which suggested that the fibrils infiltrated through the basement membrane region). The Stage 5 and 6 papillae had a column of vertical tenascin fibrils extending from the subsurface of the papilla to the interior mesenchyme corresponding exactly to the location of the mesenchymal condensation which was then forming the anlage of the ossicle in a flat bed about 100 microns from the conjunctival surface. The column of tenascin disappeared as the osteoid appeared in the ossicular bed on the 12th day of incubation but a dense accumulation of tenascin remained along the subsurface of the papilla. With the exception of tenascin fluorescence in the basal region of the Stage 4 papilla, tenascin fibrils were not observed in the other stages of papilla development in the epithelium covering areas between the mesenchymal condensation. This restricted distribution of tenascin may be important in the morphogenesis of scleral papillae and scleral ossicles.

Animals↗

PubMed1987

Tenascin is a stromal marker for epithelial malignancy in the mammary gland.

Tenascin is an extracellular matrix glycoprotein that is not present in the normal mature rat mammary gland. The distribution of tenascin was examined by immunohistochemistry in mammary tumors from carcinogen-treated and untreated rats, in virus-induced mammary tumors from mice, and in a variety of mammary gland lesions from humans. Tenascin was detectable in the stroma of the malignant but not of the benign tumors from all species. An inhibition ELISA, testing homogenates of rat tumors, confirmed that tenascin was present in malignant but not in benign tumors. Thus, tenascin was consistently found to be a stromal marker for epithelial malignancy in the mammary gland. It is concluded that tenascin may be involved in the interactions between the epithelial and mesenchyme-derived (stromal) components of the mammary gland, which are known to influence epithelial carcinogenesis in this organ.

Adenocarcinoma↗

PubMed1987

Epithelial-mesenchymal interactions in the developing kidney lead to expression of tenascin in the mesenchyme.

Tenascin, a mesenchymal extracellular matrix glycoprotein, has been implicated in epithelial-mesenchymal interactions during fetal development (Chiquet-Ehrismann, R., E. J. Mackie, C. A. Pearson, T. Sakakura, 1986, Cell, 47:131-139). We have now investigated the expression of tenascin during embryonic development of the mouse kidney. In this system, mesenchymal cells convert into epithelial cells as a result of a tissue interaction. By immunofluorescence, tenascin could not be found in the mesenchyme until kidney tubule epithelial began to form. It then became detectable around condensates and s-shaped bodies, the early stages of tubulogenesis. In an in vitro culture system, tenascin expression by the mesenchyme is tightly coupled to the de novo formation of epithelial, and does not occur if tubulogenesis is suppressed. The results strongly suggest that the formation of the new epithelium stimulates the expression of tenascin in the nearby mesenchyme. During postnatal development, the expression of tenascin decreases and the spatial distribution changes. In kidneys from adult mice, no tenascin can be found in the cortex, but interspersed patches of staining are visible in the medullary stroma. The results strongly support the view that tenascin is involved in epithelial-mesenchymal interactions. It could therefore be crucial for embryonic development.

Animals↗

PubMed1987

Tenascin is associated with chondrogenic and osteogenic differentiation in vivo and promotes chondrogenesis in vitro.

The tissue distribution of the extracellular matrix glycoprotein, tenascin, during cartilage and bone development in rodents has been investigated by immunohistochemistry. Tenascin was present in condensing mesenchyme of cartilage anlagen, but not in the surrounding mesenchyme. In fully differentiated cartilages, tenascin was only present in the perichondrium. In bones that form by endochondral ossification, tenascin reappeared around the osteogenic cells invading the cartilage model. Tenascin was also present in the condensing mesenchyme of developing bones that form by intramembranous ossification and later was present around the spicules of forming bone. Tenascin was absent from mature bone matrix but persisted on periosteal and endosteal surfaces. Immunofluorescent staining of wing bud cultures from chick embryos showed large amounts of tenascin in the forming cartilage nodules. Cultures grown on a substrate of tenascin produced more cartilage nodules than cultures grown on tissue culture plastic. Tenascin in the culture medium inhibited the attachment of wing bud cells to fibronectin-coated substrates. We propose that tenascin plays an important role in chondrogenesis by modulating fibronectin-cell interactions and causing cell rounding and condensation.

Animals↗

PubMed1987

Changes in the distribution of tenascin during tooth development.

Tenascin is an extracellular matrix molecule that was earlier shown to be enriched in embryonic mesenchyme surrounding the budding epithelium in various organs including the tooth. In the present study tenascin was localized by immunohistology throughout the course of tooth development in the mouse and rat using polyclonal antibodies against chick tenascin. The results indicate that tenascin is expressed by the lineage of dental mesenchymal cells throughout tooth ontogeny. The intensity of staining with tenascin antibodies in the dental papilla mesenchyme was temporarily reduced at cap stage when the tooth grows rapidly and undergoes extensive morphogenetic changes. During the bell stage of morphogenesis, the staining intensity increased and tenascin was accumulated in the dental pulp even after completion of crown development and eruption. Tenascin was present in the dental basement membrane at the time of odontoblast differentiation. The dental papilla cells ceased to express tenascin upon differentiation into odontoblasts and tenascin was completely absent from dentin. It can be speculated that the remarkable expression of tenascin in the dental mesenchymal cells as compared to other connective tissues is associated with their capacity to differentiate into hard-tissue-forming cells.

Animals↗

PubMed1986

Tenascin: an extracellular matrix protein involved in tissue interactions during fetal development and oncogenesis.

The extracellular matrix protein tenascin (previously described as myotendinous antigen) is selectively present in the mesenchyme surrounding fetal rat mammary glands, hair follicles, and teeth, three organ anlagen where the mesenchyme is essential for development. No tenascin is detectable in the normal adult mammary gland. Carcinogen-induced mammary tumors contained tenascin in their fibrous tissue. As reported for the molecule described as a "hexabrachion," tenascin contaminates so-called "cell-surface fibronectin," where it accounts for most of the detectable hemagglutinating activity. Of the extracellular matrix proteins compared, tenascin is the least effective substrate for attachment of primary mammary tumor cells, but the most effective in promoting cell growth after serum is removed from the culture medium.

Adenocarcinoma↗