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| | Schematic representation of a monomeric tenascin-C subunit. |
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| Description | Tenascin-C consists of structural motifs arranged in a linear order. Mammalian tenascin-C proteins contain amino-terminal heptad repeats, 14.5 EGF-like repeats, 8 constant FN III domains, whereas 9 additional FN III domains can be included in a combinatorial manner by alternative splicing, and a carboxyl-terminal fibrinogen globe. A prominent feature of tenascin-C is the assembly into hexamers, so-called hexabrachions.
The primary sequence encodes a protein of 2110 amino acids. Amino acids 1-22 represent the secretion signal, amino acids 189-621 constitute the EGF-like repeats, and amino acids 622-1882 account for the FNIII domains. SDS-Page analysis revealed a molecular weight of full-length tenascin-C of 250kDa - 300kDa per subunit under reducing conditions.
Alternative splicing within the stretch of FN III domains results in a great number and diversity in tenascin-C isoforms. |
| Expression | More than two decades ago, tenascin-C was discovered as an extracellular matrix protein (ECM) enriched in the stroma of gliomas and as a myotendinous antigen. Tenascin-C expression is highly regulated both during development and in the adult. Tenascin-C levels are high during embryogenesis, but almost absent during normal postnatal life with some basal expression detectable in tendons and ligaments only. In adult life, tenascin-C is also expressed within the sub-ventricular zone in the central nervous system, a region that constitutes the neural stem cell niche. A prominent feature of tenascin-C is its re-appearance in response to pathological situations such as infection, inflammation and tissue remodeling. Another striking example of a pathological situation leading to the re-expression of tenascin-C is the onset of tumorigenesis, where tenascin-C is specifically expressed in the activated tumor stroma. Tenascin-C can be induced by various stimuli, such as the pro- and anti-inflammatory cytokines, interleukins, TNFa or IFNg and growth factors such as TGFb , EGF or PDGF. Furthermore, tenascin-C inducing stimuli include mechanical stress, hypoxia, and reactive oxygen species, factors or conditions which also might play a prominent role in tumors. |
| Localisation | Extracellular matrix. |
| Function | Adhesion: Tenascin-C acts as an anti-adhesive substratum for a large variety of cells. Active inhibition of cell spreading was further confirmed by mixing tenascin-C together with fibronectin, which is a classical adhesion protein. Whereas cells on fibronectin nicely spread, form focal contacts and actin stress fibers, the same cells plated on a mixed fibronectin-tenascin-C substratum are not able to spread and do not form focal contacts and actin cables.
Migration: Tenascin-C enhances migration and invasiveness of different cancer cells.
Proliferation: Tenascin-C stimulates cancer cell proliferation.
Angiogenesis: Tenascin-C is expressed around angiogenic vessels in many tumors and there is evidence that it promotes and regulates angiogenesis in vitro and in vivo. Moreover, in glioma patients, clinical studies revealed an inhibition of tumor angiogenesis by applying antibodies directed against tenascin-C. |
| Homology | Tenascin-C belongs to the tenascin family, which is a highly conserved family of large oligomeric extracellular matrix proteins. Vertebrate genomes harbor four tenascin genes, which have been termed tenascin-C, tenascin-XB (TNXB), tenascin-R, and tenascin-W. |
| Human glioma-mesenchymal extracellular matrix antigen defined by monoclonal antibody. |
| Bourdon MA, Wikstrand CJ, Furthmayr H, Matthews TJ, Bigner DD. |
| Cancer Res. 1983 Jun;43(6):2796-805. |
| PMID 6342760 |
| |
| Chick myotendinous antigen II. A novel extracellular glycoprotein complex consisting of large disulfide-linked subunits. |
| Chiquet M, Fambrough DM. |
| J Cell Biol. 1984 Jun;98(6):1937-46. |
| PMID 6202699 |
| |
| Tenascin interferes with fibronectin action. |
| Chiquet-Ehrismann R, Kalla P, Pearson CA, Beck K, Chiquet M. |
| Cell. 1988 May 6;53(3):383-90. |
| PMID 2452695 |
| |
| Tenascin-C in serum: a questionable tumor marker. |
| Schenk S, Muser J, Vollmer G, Chiquet-Ehrismann R. |
| Int J Cancer. 1995 May 16;61(4):443-9. |
| PMID 7538974 |
| |
| Tenascin-C expression by angiogenic vessels in human astrocytomas and by human brain endothelial cells in vitro. |
| Zagzag D, Friedlander DR, Dosik J, et al. |
| Cancer Res. 1996 Jan 1;56(1):182-9. |
| PMID 8548761 |
| |
| The Tenascin family of ECM Glycoproteins: Structure, Function, and Regulation Durig Embryonic Development and Tissue Remodeling. |
| Jones FS and Jones PL. |
| Dev Dyn. 2000 Jun;218(2):235-59. (REVIEW) |
| PMID 10842355 |
| |
| Tenascins: regulation and putative functions during pathological stress. |
| Chiquet-Ehrismann R, Chiquet M. |
| J Pathol. 2003 Jul;200(4):488-99. (REVIEW) |
| PMID 12845616 |
| |
| Coding SNP in tenascin-C Fn-III-D domain associates with adult asthma. |
| Matsuda A, Hirota T, Akahoshi M, et al. |
| Human Molecular Genetics. 2005 Oct 1;14(19):2779-86. |
| PMID 16115819 |
| |
| Genes that mediate breast cancer metastasis to lung. |
| Minn A, Gupta GP, Siegel PM, et al. |
| Nature. 2005 Jul 28;436(7050):518-24. |
| PMID 16049480 |
| |
| Potential oncogenic action of tenascin-C in tumorigenesis. |
| Orend G. |
| Int J Biochem Cell Biol. 2005 May;37(5):1066-83. (REVIEW) |
| PMID 15743679 |
| |
| Vascular tenascin-C regulates cardiac endothelial phenotype and neovascularization. |
| Ballard VL, Sharma A, Duignan I, et al. |
| Faseb J. 2006 Apr;20(6):717-9. |
| PMID 16461331 |
| |
| Tenascin-C induced signaling in cancer. |
| Orend G and Chiquet-Ehrismann R. |
| Cancer Lett. 2006 Dec 8;244(2):143-63. (REVIEW) |
| PMID 16632194 |
| |
| Endogenous human microRNAs that suppress breast cancer metastasis. |
| Tavazoie SF, Alarcon C, Oskarsson T, et al. |
| Nature. 2008 Jan 10;451(7175):147-52. |
| PMID 18185580 |
| |
