The human placenta: a model for tenascin expression

Summary Tenascin is a large glycoprotein of the extracellular matrix. Previous reports have demonstrated that it is associated with epithelial-mesenchymal interfaces and is expressed during embryonic and tumour development, wound healing, cell proliferation and it may be involved in immunomodulation. The human placenta shows numerous features related to these aspects. We have investigated the presence of tenascin in the human placenta throughout pregnancy by immunohistochemistry. We used monoclonal (mAb) and polyclonal (pAb) antibodies to tenascin, a mAb to fibrin, a pAb to fibrinogen, and the mAb Ki-67 as proliferation marker. Tenascin was highly expressed in the mesenchymal villi which are considered the basis of growth and differentiation of the villous trees. Moreover, fibrinoid deposits at the surfaces of the villous trees were always separated from the fetal stroma by tenascin. The stroma of villi encased in fibrinoid was also positive for tenascin. This glycoprotein was also expressed in the villous stroma directly apposed to cell islands and cell columns. In the proximal portions of both epithelial structures, cytotrophoblast was Ki-67 positive. These data show that tenascin is expressed during the development of the placenta, particularly in the mesenchymal villi, cell islands and cell columns. These structures are considered to be the proliferating units of the villous trees. Tenascin underlying fibrinoid deposits suggests that it also participates in repair mechanisms. Thus, in the human placenta tenascin expression can be correlated with villous growth, cell proliferation, and fibrinoid deposition. Its role in immunoprotection of fetal tissues in areas where syncytiotrophoblast as barrier is missing or damaged is discussed.     

Binding of antibodies against high and low molecular weight cytokeratin proteins in the human placenta with special reference to infarcts, proliferation and differentiation processes

Recent immunocytochemical studies have shown that placental villous trophoblasts contain the high molecular weight cytokeratin (CK) proteins 5/6 and 17. In the case of CK 17, trophoblastic immunostaining was positive in villi covered by fibrinoid. CKs 5/6 and 17 are expressed by hyperproliferative cells. The aim of this investigation was to examine the location of these CKs in placental infarcts, known to be demarcated by fibrinoid and hyperproliferative trophoblasts. The results were compared with those obtained by immunostaining against Ki-67, tenascin and α1-, α6- and β1- integrins, which are involved in cell proliferation, differentiation and regenerative processes. Furthermore, the expression of the single CKs 7, 8, 10, 13, 14, 18 and 19 was investigated by immunocytochemistry and immunoblotting. While low and high molecular weight CKs were present in villous and extravillous trophoblasts, only low molecular weight CKs were detected in vascular and extravascular placental smooth muscle cells. Placental infarcts revealed different immunoreactivities in the infarct margin and centre: high molecular CKs, tenascin, Ki-67 and oncofoetal fibronectin predominated in the infarct margin, low molecular CKs, fibrin and integrins in the centre. The expression of tenascin and a defined change in the expression of CK 17 indicates villous repair and hyperproliferative mechanisms in placental infarcts. This revised version was published online in November 2006 with corrections to the Cover Date.     

Binding of antibodies against high and low molecular weight cytokeratin proteins in the human placenta with special reference to infarcts, proliferation and differentiation processes

Recent immunocytochemical studies have shown that placental villous trophoblasts contain the high molecular weight cytokeratin (CK) proteins 5/6 and 17. In the case of CK 17, trophoblastic immunostaining was positive in villi covered by fibrinoid. CKs 5/6 and 17 are expressed by hyperproliferative cells. The aim of this investigation was to examine the location of these CKs in placental infarcts, known to be demarcated by fibrinoid and hyperproliferative trophoblasts. The results were compared with those obtained by immunostaining against Ki-67, tenascin and α1-, α6- and β1- integrins, which are involved in cell proliferation, differentiation and regenerative processes. Furthermore, the expression of the single CKs 7, 8, 10, 13, 14, 18 and 19 was investigated by immunocytochemistry and immunoblotting. While low and high molecular weight CKs were present in villous and extravillous trophoblasts, only low molecular weight CKs were detected in vascular and extravascular placental smooth muscle cells. Placental infarcts revealed different immunoreactivities in the infarct margin and centre: high molecular CKs, tenascin, Ki-67 and oncofoetal fibronectin predominated in the infarct margin, low molecular CKs, fibrin and integrins in the centre. The expression of tenascin and a defined change in the expression of CK 17 indicates villous repair and hyperproliferative mechanisms in placental infarcts. This revised version was published online in November 2006 with corrections to the Cover Date.     

Hyaluronate and CD44 expression patterns in the human placenta throughout pregnancy

Hyaluronan (HA) and CD44 are involved in several processes such as cell migration and differentiation. In the present study, we examined the expression and distribution of both hyaluronan and its cell surface receptor (CD44) in the human placenta, which is a rapidly growing and differentiating organ that plays a fundamental role in fetal life. Hyaluronan was detected by a specific biotinylated binding probe, termed b-PG. In the first half of gestation, HA was strongly expressed in the stroma of the mesenchymal villi which have been previously identified as responsible for the growth and differentation of the villous trees. The other villous types showed an intense staining only in the fetal vessel walls and in the connective tissue closely underlying the trophoblastic cover. In addition, hyaluronan positive staining was also apparent in a restricted rim of villous stroma directly apposed to extravillous cytotrophoblastic cell islands and cell columns. In full term placentas, all villi expressed HA in their stromal tissue with a more homogenous staining than in the first half of gestation. In contrast to hyaluronan, in the first trimester CD44 was restricted to some of the Hofbauer cells which may be able to internalize hyaluronan, thus playing a significant role in its removal in early pregnancy. CD44 was primarily expressed starting from the 16th week of gestation. At the end of pregnancy it was expressed in the various villous types, especially in stem villi. Moreover, the plasma membrane of some extravillous cytotrophoblastic cells in the basal plate and the large majority of the decidual cells showed a positive immunostaining for this receptor. Taken together, these data suggest that HA is strongly involved in early villous morphogenesis, whereas CD44 seem to be play an important role in tissue remodelling later in gestation.     

Sequential induction of syndecan, tenascin and cell proliferation associated with mesenchymal cell condensation during early tooth development

The cell surface proteoglycan, syndecan, and the extracellular matrix glycoprotein, tenascin, are expressed in the mesenchyme during early development of many organs. We have studied the expression patterns of syndecan and tenascin during initiation of tooth development and in association with mesenchymal cell condensation and compared these with cell proliferation. Syndecan, tenascin and bromodeoxyuridine (BrdU) incorporation were localized by triple-labelling immunohistochemistry in serial sections of molar tooth germs of mouse embryos. Prior to formation of the epithelial tooth bud, syndecan accumulated in the mesenchymal cells which underlie the presumptive dental epithelium, but tenascin was not detected at this stage. Tenascin appeared during initiation of the epithelial down-growth at the lingual aspect of the tooth germ. During subsequent formation of the epithelial bud, at the late bud stage, syndecan and tenascin became exactly colocalized in the condensed mesenchyme which was clearly demarcated from other jaw mesenchyme. The expression of syndecan and tenascin was accompanied by rapid cell proliferation as indicated by marked BrdU incorporation. When development advanced to the cap stage, syndecan staining intensity in the dental papilla mesenchyme increased further whereas tenascin became reduced. In conclusion, the results demonstrate that the expression patterns of syndecan and tenascin overlap transiently during the period of mesenchymal cell condensation and that this is accompanied by cell proliferation. Syndecan and tenascin may play a role in growth control and in compartmentalization of the dental mesenchymal cells in the condensate.     

Expression of tenascin in bile duct cancer of hamster liver by combined treatment of dimethylnitrosamine with Opisthorchis viverrini infections

Tenascin is an extracellular matrix glycoprotein known to be an essential factor for the modulation of reciprocal interactions between the epithelium and mesenchyme during embryogenesis and tumourigenesis. The interactions between the expression of tenascin in the liver of Syrian golden hamster and the development of bile duct cancer in an Opisthorchis viverrini-associated cholangiocarcinoma model were investigated. The tenascin was expressed in connective tissues surrounding the dilated ducts, ductal rims and the stroma of cancers, and strongly in the stroma flame of necrotic cancer nodules. The mRNA signal for tenascin was also recognized in the stroma cells. The potential roles of tenascin as prognostic tumour markers are discussed.     

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.     

Tenascin mediates cell attachment through an RGD-dependent receptor

Tenascin is an extracellular matrix glycoprotein expressed in association with mesenchymal-epithelial interactions during development and in the neovasculature and stroma of undifferentiated tumors. This selective expression of tenascin indicates a specific role in cell matrix interactions. We now show that tenascin can support the adhesion of a variety of cell types, including various human tumor cells, normal fibroblasts, and endothelial cells, all of which can attach to a substrate coated with tenascin. Detailed studies on the mechanism of the tenascin-promoted cell attachment were carried out with the human glioma cell line U251MG. The attachment of these cells and others to tenascin were inhibited specifically by peptides containing the RGD cell attachment signal. Affinity chromatography procedures similar to those that have been used to isolate other adhesion receptors yielded a heterodimeric cell surface protein which bound to a tenascin affinity matrix in an RGD-dependent fashion. One of the subunits of this putative tenascin receptor comigrates with the beta subunit of the fibronectin receptor in SDS-PAGE and cross reacts with antibodies prepared against the fibronectin receptor in immunoblotting. These results identify the tenascin receptor as a member of the fibronectin receptor family within the integrin superfamily of receptors. The cell attachment response on tenascin is distinctly different from that seen on fibronectin, suggesting that cell adhesion and motility may be modulated at those sites where tenascin is expressed in the extracellular matrix.     

Downregulation of tenascin expression by glucocorticoids in bone marrow stromal cells and in fibroblasts

Tenascin, a predominantly mesenchymal extracellular matrix (ECM) glycoprotein has a rather restricted tissue distribution, but until now factors that inhibit its expression have not been identified. Glucocorticoids are known to be beneficial for establishment of myelopoiesis in long-term bone marrow cultures. Tenascin was found to be expressed in the bone marrow, and glucocorticoids were found to affect bone marrow tenascin expression. Both tenascin mRNAs and the mRNA of another ECM protein, laminin B1 chain, were drastically downregulated by glucocorticoids during initiation of bone marrow cultures. However, in already established long-term cultures glucocorticoids did not affect laminin B1 chain mRNA levels although tenascin mRNAs continued to be downregulated. Studies with a stromal cell line (MC3T3-G2/PA6) and fibroblasts (3T3) suggested that glucocorticoids act directly on the stromal cells that produce tenascin. In 3T3 cells this downregulation occurred within 12 h of glucocorticoid-treatment, suggesting that glucocorticoids acted through cis regulatory elements of the tenascin gene. We suggest that glucocorticoids in part regulate hematopoiesis by modifying the ECM. Furthermore, downregulation of tenascin expression by glucocorticoids may in part explain the restricted tissue distribution of tenascin in other tissues.     

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.     

Exogenous tenascin inhibits mesodermal cell migration during amphibian gastrulation.

We have used amphibian gastrulation as a model system to study the action of the extracellular matrix (ECM) glycoprotein tenascin on mesodermal cell migration. Tenascin function was assayed in vitro during spreading of isolated cells from the dorsal marginal zone (DMZ) and during cell migration from DMZ explants. Plastic coated with bovine fibronectin or gastrula ECM was used as a substratum. In both cases, tenascin added to the medium inhibited spreading and migration of mesodermal cells. In addition, a substratum coated with a mixture of fibronectin and tenascin was found to prevent mesodermal cell migration. Tenascin was also microinjected into the blastocoel cavity of living embryos at the late blastula stage. This led to a complete arrest of gastrulation in more than 80% of the cases. Scanning electron microscopy of fractures from arrested gastrulae showed that mesodermal cell migration was blocked. Similar injection experiments carried out at the middle gastrula stage demonstrated that tenascin is able to inhibit cell migration after cells have already contacted the ECM. Mesodermal cell migration in the presence of tenascin could be restored in vitro and in vivo by the monoclonal antibody mAb Tn68 which is known to mask a cell binding site of the molecule. Finally, tenascin microinjected into the blastocoel of blastula or gastrula stage embryos bound within 15 min to the ECM fibrils at all the stages studied. Our results show that exogenous tenascin can be incorporated into embryonic ECM and interferes in vivo with the interactions of cells with a fibronectin-rich matrix.     

Stimulation of tenascin expression in mesenchyme by epithelial-mesenchymal interactions

Tenascin is an extracellular matrix glycoprotein with an unusually restricted tissue distribution in the developing embryo. The protein was independently discovered by several investigators, and has been given many different names. Synonyms of tenascin include cytotactin, J1, hexabrachion and glioma-mesenchymal extracellular matrix antigen. Whereas fibronectin is expressed rather uniformly in matrices of embryonic mesenchyme, tenascin is found in the mesenchyme at sites of epithelial-mesenchymal interactions. Tenascin is thus found close to epithelial basement membranes but it is probably not an integral basement membrane component. The distribution suggests that developing epithelial cells may produce locally active factors that stimulate tenascin synthesis in the nearby mesenchyme. Tenascin is composed of disulfide-bonded subunits of approximate Mr between 200-280 kD. Using monoclonal antibodies to mouse tenascin, we find two major subunits of Mr 260 and 200 kD from mouse fibroblasts. Work from many laboratories suggests that the different subunits arise by differential splicing of one mRNA. Rotary shadowing electron microscopy of the intact molecule suggests a six-armed structure connected by a central region. However, the different subunits are not co-ordinately expressed during embryogenesis, suggesting that tenascin can exist as different isoforms. The different isoforms may serve distinct functions. The function of tenascin is not well known, but it has been suggested that it alters the adhesive properties of cells and causes cell rounding.     

Development of cytotrophoblast columns from explanted first-trimester human placental villi: role of fibronectin and integrin alpha5beta1

Human first-trimester floating mesenchymal villi explanted onto gels of collagen I or Matrigel were observed to undergo de novo development of anchoring sites. These consisted of cytotrophoblast columns that formed by proliferation of stem villous cytotrophoblast cells, as revealed by whole-mount and thin-section microscopy and incorporation of bromodeoxyuridine into DNA. Column formation occurred exclusively at the distal tips of the villi. No column formation was observed in tissue explanted onto agarose. On Matrigel, the developing columns penetrated downwards into the matrix, whereas on collagen I, cytotrophoblast sheets spread across the surface of the gel and merged to form a shell. The developing columnar cytotrophoblast up-regulated integrins alpha1beta1 and alpha5beta1 and produced an extracellular matrix containing oncofetal fibronectin, as in vivo. Function-blocking antibodies were used to investigate the role of the integrin-fibronectin interaction in anchoring villus development on collagen I. Antibodies to fibronectin and the integrin subunits alpha5 and beta1, added at 24 h, all changed the pattern of cytotrophoblast outgrowth. Anti-fibronectin caused cell rounding within the cytotrophoblast sheet and increased the population of single cells at its periphery. Anti-integrin alpha5 caused rounding and redistribution of cells within the outgrowth. In the presence of anti-integrin beta1, cell-collagen interactions within the sheet were destabilized, often leading to the appearance of an annulus of aggregated cells at the periphery. These results show that 1) mesenchymal villi retain the potential to form anchoring sites until at least the end of the first trimester, 2) adhesion to a permissive extracellular matrix stimulates cytotrophoblast proliferation and differentiation along the extravillous lineage, 3) integrin alpha5beta1-fibronectin interactions contribute significantly to anchorage of the placenta to uterine extracellular matrix. We suggest that as the developing placenta ramifies, new sites of anchorage form whenever peripheral villi contact decidua. This process is predicted to contribute to the stability of the placental-decidual interface.     

Tenascin during gut development: appearance in the mesenchyme, shift in molecular forms, and dependence on epithelial-mesenchymal interactions [published erratum appears in J Cell Biol 1989 Mar;108(3):following 1175]

Tenascin, an extracellular matrix protein, is expressed in the mesenchyme around growing epithelia in the embryo. We therefore investigated whether epithelial cells can stimulate expression of tenascin in embryonic mesenchyme. Mesenchyme from the presumptive small intestine was used because it is known that reciprocal epithelial- mesenchymal interactions are important for gut morphogenesis. Rat monoclonal antibodies against mouse tenascin were raised and were found to react specifically with mouse tenascin in ELISA. In supernatants of cultured fibroblasts, the antibodies precipitated two peptides of Mr 260 and 210 kD. One of the antibodies also reacted with these tenascin chains in immunoblots of tissue extracts. We found that tenascin was absent during early stages of gut development, at stages when the mesenchyme is already in contact with the stratified epithelium of the endoderm. Rather, it appeared in the mesenchyme when the homogenous endodermal epithelium differentiated into the heterogenous absorptive epithelium. Tenascin remained present in the stroma of the adult gut, close to the migration pathways of the continuously renewing epithelium. When first detected during intestinal differentiation, the 210-kD component was predominant but at birth the relative amount of the 260-kD component had increased. The expression data suggested that the appearance of tenascin in the mesenchyme was dependent on the presence of epithelium. To test this, isolated gut mesenchymes from 13- d-old mouse embryos were cultured for 24 h either alone or together with epithelial and nonepithelial cells. Whereas mesenchyme cultured alone or in the presence of nonepithelial B16-F1 melanoma cells produced only trace amounts of tenascin, expression was strongly stimulated by the epithelial cell line, Madin-Darby canine kidney (MDCK). We propose that growing and differentiating epithelia produce locally active factors which stimulate synthesis of tenascin in the surrounding mesenchyme.     

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.     

Tenascin is a cytoadhesive extracellular matrix component of the human hematopoietic microenvironment

Tenascin is a large extracellular matrix (ECM) glycoprotein found in restricted tissue locations in the adult organism. It is copiously synthesized in regenerative organs or regenerating tissues and by certain tumors. We have analyzed the expression of tenascin in human long term bone marrow cultures as well as in cryostat sections of native bone marrow and found it strongly expressed by the stromal cells of the microenvironment. Two different protein subunits of 280 and 220 kD were detected by immunoblotting. These two forms are derived most likely from two different mRNA splice variants of 6 and 8 kb detected by Northern blotting. The in vivo analysis of cryostat sections showed a codistribution with other ECM molecules such as fibronectin and collagen type III in the microenvironment surrounding the maturing hematopoietic cells. Using two independent cell adhesion assays tenascin could be shown to function as a cytoadhesive molecule for hematopoietic cells. These data suggest a direct involvement of tenascin in the retention of hematopoietic progenitor cells in the stroma.     

Close correlation between the distribution of tenascin and that of actin filaments in the mouse urethral mesenchyme during active morphogenesis.

The distribution of tenascin, an extracellular matrix glycoprotein, and that of actin filaments were studied in the developing urethra of mouse embryos by antitenascin immunofluorescent and rhodamine-phalloidin staining. Tenascin appeared transiently in the urethral mesenchyme at the site of active morphogenesis in which the urethral epithelium separated from the surface epithelia of the glans and prepuce, being tubular, and the bilateral mesenchymes lining the preexisting urethral epithelium were seamed together in the ventral side of the tubular urethra immediately after the epithelial separation. The spatially and temporally restricted distribution of tenascin corresponded well to that of mesenchymal cells which possessed many actin filaments. These observations suggest that tenascin is involved in the cytoskeletal organization of mesenchymal cells in the active phase of morphogenesis.     

Tenascin distribution in the normal human breast is altered during the menstrual cycle and in carcinoma

Tenascin is a novel extracellular matrix glycoprotein which appears to have a major role in tissue development. Previous studies have stated that tenascin is absent from the normal human, rat and mouse breast, its distribution being restricted to embryonic and malignant mammary tissues. No previous studies have investigated tenascin distribution as a function of the normal menstrual cycle. Therefore this study addresses the cyclical appearance of tenascin in the normal breast and associated changes in distribution in preinvasive cancer (carcinoma-in-situ) and invasive infiltrating ductal carcinoma. Tenascin is present in the normal human adult mammary gland, principally in the basement membrane, sub-basement-membrane zone and delimiting layer of fibroblasts around the ductules. Both the distribution and quantity of tenascin change during the menstrual cycle. In carcinoma-in-situ (preinvasive cancer) tenascin is present in the attenuated basement membrane/sub-basement-membrane zone around the expanded ductules and in small amounts in the stroma. In infiltrating ductal carcinoma, tenascin is absent from the remnants of the basement membrane and sub-basement-membrane zone but greatly increased in the adjacent intralobular and interlobular stroma. Therefore, if tenascin is used as a basement membrane/sub-basement-membrane marker for distinguishing carcinoma-in-situ from invasive ductal carcinoma, the time of the menstrual cycle is of importance in interpreting the biopsy appearance. This study suggests that the optimal time for biopsy is between weeks 3 and 4 of the cycle, to avoid confusion between the normal low levels of tenascin (due to hormonal status) and those due to microinvasive disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Distribution of collagen types III and IV in human placental villi

Immunofluorescent examination showed more significant accumulation of interstitial collagen type III in the stroma of mature placenta compared with immature one. Localization of membrane collagen type IV was found neither in basal membranes of epithelium and villous vessels of mature term placenta, nor in their stroma. The described patterns of distribution of collagen types III and IV in human placenta villi were proved by immunoelectronmicroscopic method.     

What distinguishes tenascin from fibronectin?

Tenascin and fibronectin are two major extracellular matrix glycoproteins. They both consist of large disulfide-linked subunits composed of multiple structural domains. More than half of each molecule consists of so-called fibronectin type III repeats, but the other domains differ. Fibronectin is a dimer, whereas tenascin is a hexamer. Often fibronectin and tenascin are colocalized in tissues, but the occurrence of tenascin is much more restricted when compared with fibronectin. Tenascin is transiently expressed in many developing organs such as connective tissues, the mesenchyme of epithelial organs, and also the central and peripheral nervous systems, and it reappears in the stroma of many tumors. The distinctive and highly regulated expression of tenascin has provoked interest in trying to identify possible functions of tenascin in cell-cell and cell-substratum adhesion, cell migration, growth, and cell differentiation during morphogenesis.