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Tenascin-C is expressed by human glioma in vivo and shows a strong association with tumor blood vessels

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Abstract

The extracellular matrix (ECM) protein tenascin-C (TN-C) is upregulated within glioma tissues and cultured glioma cell lines. TN-C possesses a multi-modular structure and a variety of functional properties have been reported for its domains. We describe five novel monoclonal antibodies identifying different domains of TN-C. The epitopes for these antibodies were investigated by using recombinantly expressed fibronectin type III domains of TN-C. The biological effects of TN-C fragments on glioma cell proliferation and adhesion were analyzed. The expression pattern of TN-C in human glioma tissue sections and in glioma cell lines was studied with the novel library of monoclonal antibodies. The immunocytochemical analyses of the established human glioma cell lines U-251-MG, U-373-MG and U-87-MG revealed distinct staining patterns for each antibody. Robust expression of TN-C was found within the tumor mass of surgery specimens from glioblastoma. In many cases, the expression of this ECM molecule was clearly associated with blood vessels, particularly with microvessels. Three of the new antibodies highlighted individual TN-C-expressing single cells in glioma tissues. The effect of TN-C domains on glioma cells was examined by a BrdU-proliferation assay and an adhesion assay. Short fragments of constitutively expressed TN-C-domains did not exert significant effects on the proliferation of glioma cells, whereas the intact molecule increased cell division rates. In contrast, the long fragment TNfnALL containing all of the FNIII domains of TN-C decreased proliferation. Additionally, we found strong differences between the adhesion-influencing properties of the recombinant fragments on glioma cells.

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References

  • Adair-Kirk TL, Senior RM (2008) Fragments of extracellular matrix as mediators of inflammation. Int J Biochem Cell Biol 40:1101–1110

    PubMed  CAS  Google Scholar 

  • Adams M, Jones JL, Walker RA, Pringle JH, Bell SC (2002) Changes in tenascin-C isoform expression in invasive and preinvasive breast disease. Cancer Res 62:3289–3297

    PubMed  CAS  Google Scholar 

  • Allen M, Jones JL (2011) Jekyll and Hyde: the role of the microenvironment on the progression of cancer. J Pathol 223:162–176

    PubMed  CAS  Google Scholar 

  • Aukhil I, Joshi P, Yan Y, Erickson HP (1993) Cell- and heparin-binding domains of the hexabrachion arm identified by tenascin expression proteins. J Biol Chem 268:2542–2553

    PubMed  CAS  Google Scholar 

  • Behrem S, Zarkovic K, Eskinja N, Jonjic N (2005) Distribution pattern of tenascin-C in glioblastoma: correlation with angiogenesis and tumor cell proliferation. Pathol Oncol Res 11:229–235

    PubMed  CAS  Google Scholar 

  • Borsi L, Carnemolla B, Nicolo G, Spina B, Tanara G, Zardi L (1992) Expression of different tenascin isoforms in normal, hyperplastic and neoplastic human breast tissues. Int J Cancer 52:688–692

    PubMed  CAS  Google Scholar 

  • Bosman FT, Stamenkovic I (2003) Functional structure and composition of the extracellular matrix. J Pathol 200:423–428

    PubMed  CAS  Google Scholar 

  • Bourdon MA, Wikstrand CJ, Furthmayr H, Matthews TJ, Bigner DD (1983) Human glioma-mesenchymal extracellular matrix antigen defined by monoclonal antibody. Cancer Res 43:2796–2805

    PubMed  CAS  Google Scholar 

  • Brellier F, Chiquet-Ehrismann R (2012) How do tenascins influence the birth and life of a malignant cell? J Cell Mol Med 16:32–40

    PubMed  CAS  Google Scholar 

  • Brellier F, Tucker RP, Chiquet-Ehrismann R (2009) Tenascins and their implications in diseases and tissue mechanics. Scand J Med Sci Sports 19:511–519

    PubMed  CAS  Google Scholar 

  • Carnemolla B, Castellani P, Ponassi M, Borsi L, Urbini S, Nicolo G, Dorcaratto A, Viale G, Winter G, Neri D, Zardi L (1999) Identification of a glioblastoma-associated tenascin-C isoform by a high affinity recombinant antibody. Am J Pathol 154:1345–1352

    PubMed  CAS  Google Scholar 

  • Carpenter PM, Dao AV, Arain ZS, Chang MK, Nguyen HP, Arain S, Wang-Rodriguez J, Kwon SY, Wilczynski SP (2009) Motility induction in breast carcinoma by mammary epithelial laminin 332 (laminin 5). Mol Cancer Res 7:462–475

    PubMed  CAS  Google Scholar 

  • Chiquet-Ehrismann R, Chiquet M (2003) Tenascins: regulation and putative functions during pathological stress. J Pathol 200:488–499

    PubMed  CAS  Google Scholar 

  • Chi-Rosso G, Gotwals PJ, Yang J, Ling L, Jiang K, Chao B, Baker DP, Burkly LC, Fawell SE, Koteliansky VE (1997) Fibronectin type III repeats mediate RGD-independent adhesion and signaling through activated beta1 integrins. J Biol Chem 272:31447–31452

    PubMed  CAS  Google Scholar 

  • Chung CY, Murphy-Ullrich JE, Erickson HP (1996) Mitogenesis, cell migration, and loss of focal adhesions induced by tenascin-C interacting with its cell surface receptor, annexin II. Mol Biol Cell 7:883–892

    PubMed  CAS  Google Scholar 

  • Clark RA, Erickson HP, Springer TA (1997) Tenascin supports lymphocyte rolling. J Cell Biol 137:755–765

    PubMed  CAS  Google Scholar 

  • Day JM, Olin AI, Murdoch AD, Canfield A, Sasaki T, Timpl R, Hardingham TE, Aspberg A (2004) Alternative splicing in the aggrecan G3 domain influences binding interactions with tenascin-C and other extracellular matrix proteins. J Biol Chem 279:12511–12518

    PubMed  CAS  Google Scholar 

  • Derr LB, Chiquet-Ehrismann R, Gandour-Edwards R, Spence J, Tucker RP (1997) The expression of tenascin-C with the AD1 variable repeat in embryonic tissues, cell lines and tumors in various vertebrate species. Differentiation 62:71–82

    PubMed  CAS  Google Scholar 

  • Deryugina EI, Bourdon MA (1996) Tenascin mediates human glioma cell migration and modulates cell migration on fibronectin. J Cell Sci 109:643–652

    PubMed  CAS  Google Scholar 

  • Dobbertin A, Czvitkovich S, Theocharidis U, Garwood J, Andrews MR, Properzi F, Lin R, Fawcett JW, Faissner A (2010) Analysis of combinatorial variability reveals selective accumulation of the fibronectin type III domains B and D of tenascin-C in injured brain. Exp Neurol 225:60–73

    PubMed  CAS  Google Scholar 

  • Downward J (1998) Mechanisms and consequences of activation of protein kinase B/Akt. Curr Opin Cell Biol 10:262–267

    PubMed  CAS  Google Scholar 

  • Dueck M, Riedl S, Hinz U, Tandara A, Möller P, Herfarth C, Faissner A (1999) Detection of tenascin-C isoforms in colorectal mucosa, ulcerative colitis, carcinomas and liver metastases. Int J Cancer 82:477–483

    PubMed  CAS  Google Scholar 

  • Dunn IF, Heese O, Black PM (2000) Growth factors in glioma angiogenesis: FGFs, PDGF, EGF, and TGFs. J Neurooncol 50:121–137

    PubMed  CAS  Google Scholar 

  • Faissner A, Kruse J (1990) J1/tenascin is a repulsive substrate for central nervous system neurons. Neuron 5:627–637

    PubMed  CAS  Google Scholar 

  • Friedlander DR, Zagzag D, Shiff B, Cohen H, Allen JC, Kelly PJ, Grumet M (1996) Migration of brain tumor cells on extracellular matrix proteins in vitro correlates with tumor type and grade and involves alphaV and beta1 integrins. Cancer Res 56:1939–1947

    PubMed  CAS  Google Scholar 

  • Galoian KA, Garamszegi N, Garamszegi SP, Scully SP (2007) Molecular mechanism of tenascin-C action on matrix metalloproteinase-1 invasive potential. Exp Biol Med (Maywood) 232:515–522

    CAS  Google Scholar 

  • Garcion E, Faissner A, ffrench-Constant C (2001) Knockout mice reveal a contribution of the extracellular matrix molecule tenascin-C to neural precursor proliferation and migration. Development 128:2485–2496

    PubMed  CAS  Google Scholar 

  • Garwood J, Theocharidis U, Calco V, Dobbertin A, Faissner A (2012) Existence of tenascin-C isoforms in rat that contain the alternatively spliced AD1 domain are developmentally regulated during hippocampal development. Cell Mol Neurobiol 32:279–287

    PubMed  CAS  Google Scholar 

  • Ghert MA, Jung ST, Qi W, Harrelson JM, Erickson HP, Block JA, Scully SP (2001a) The clinical significance of tenascin-C splice variant expression in chondrosarcoma. Oncology 61:306–314

    PubMed  CAS  Google Scholar 

  • Ghert MA, Qi WN, Erickson HP, Block JA, Scully SP (2001b) Tenascin-C splice variant adhesive/anti-adhesive effects on chondrosarcoma cell attachment to fibronectin. Cell Struct Funct 26:179–187

    PubMed  CAS  Google Scholar 

  • Giese A, Rief MD, Loo MA, Berens ME (1994) Determinants of human astrocytoma migration. Cancer Res 54:3897–3904

    PubMed  CAS  Google Scholar 

  • Gilcrease MZ, Zhou X, Lu X, Woodward WA, Hall BE, Morrissey PJ (2009) Alpha6beta4 integrin crosslinking induces EGFR clustering and promotes EGF-mediated Rho activation in breast cancer. J Exp Clin Cancer Res 28:67

    PubMed  Google Scholar 

  • Götz B, Scholze A, Clement A, Joester A, Schütte K, Wigger F, Frank R, Spiess E, Ekblom P, Faissner A (1996) Tenascin-C contains distinct adhesive, anti-adhesive, and neurite outgrowth promoting sites for neurons. J Cell Biol 132:681–699

    PubMed  Google Scholar 

  • Guttery DS, Hancox RA, Mulligan KT, Hughes S, Lambe SM, Pringle JH, Walker RA, Jones JL, Shaw JA (2010a) Association of invasion-promoting tenascin-C additional domains with breast cancers in young women. Breast Cancer Res 12:R57

    PubMed  Google Scholar 

  • Guttery DS, Shaw JA, Lloyd K, Pringle JH, Walker RA (2010b) Expression of tenascin-C and its isoforms in the breast. Cancer Metastasis Rev 29:595–606

    PubMed  CAS  Google Scholar 

  • Hancox RA, Allen MD, Holliday DL, Edwards DR, Pennington CJ, Guttery DS, Shaw JA, Walker RA, Pringle JH, Jones JL (2009) Tumour-associated tenascin-C isoforms promote breast cancer cell invasion and growth by matrix metalloproteinase-dependent and independent mechanisms. Breast Cancer Res 11:R24

    PubMed  Google Scholar 

  • Harlow E, Lane D (1988) Antibodies: a laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbot, NY

    Google Scholar 

  • Haugh JM, Huang AC, Wiley HS, Wells A, Lauffenburger DA (1999) Internalized epidermal growth factor receptors participate in the activation of p21(ras) in fibroblasts. J Biol Chem 274:34350–34360

    PubMed  CAS  Google Scholar 

  • He J, Liu Y, Xie X, Zhu T, Soules M, DiMeco F, Vescovi AL, Fan X, Lubman DM (2010) Identification of cell surface glycoprotein markers for glioblastoma-derived stem-like cells using a lectin microarray and LC-MS/MS approach. J Proteome Res 9:2565–2572

    PubMed  CAS  Google Scholar 

  • Hindermann W, Berndt A, Borsi L, Luo X, Hyckel P, Katenkamp D, Kosmehl H (1999) Synthesis and protein distribution of the unspliced large tenascin-C isoform in oral squamous cell carcinoma. J Pathol 189:475–480

    PubMed  CAS  Google Scholar 

  • Hirata E, Arakawa Y, Shirahata M, Yamaguchi M, Kishi Y, Okada T, Takahashi JA, Matsuda M, Hashimoto N (2009) Endogenous tenascin-C enhances glioblastoma invasion with reactive change of surrounding brain tissue. Cancer Sci 100:1451–1459

    PubMed  CAS  Google Scholar 

  • Iyer AK, Tran KT, Borysenko CW, Cascio M, Camacho CJ, Blair HC, Bahar I, Wells A (2007) Tenascin cytotactin epidermal growth factor-like repeat binds epidermal growth factor receptor with low affinity. J Cell Physiol 211:748–758

    PubMed  CAS  Google Scholar 

  • Joester A, Faissner A (1999) Evidence for combinatorial variability of tenascin-C isoforms and developmental regulation in the mouse central nervous system. J Biol Chem 274:17144–17151

    PubMed  CAS  Google Scholar 

  • Joester A, Faissner A (2001) The structure and function of tenascins in the nervous system. Matrix Biol 20:13–22

    PubMed  CAS  Google Scholar 

  • Jones PL, Crack J, Rabinovitch M (1997) Regulation of tenascin-C, a vascular smooth muscle cell survival factor that interacts with the alpha v beta 3 integrin to promote epidermal growth factor receptor phosphorylation and growth. J Cell Biol 139:279–293

    PubMed  CAS  Google Scholar 

  • Kawataki T, Yamane T, Naganuma H, Rousselle P, Anduren I, Tryggvason K, Patarroyo M (2007) Laminin isoforms and their integrin receptors in glioma cell migration and invasiveness: evidence for a role of alpha5-laminin(s) and alpha3beta1 integrin. Exp Cell Res 313:3819–3831

    PubMed  CAS  Google Scholar 

  • Kearney JF, Radbruch A, Liesegang B, Rajewsky K (1979) A new mouse myeloma cell line that has lost immunoglobulin expression but permits the construction of antibody-secreting hybrid cell lines. J Immunol 123:1548–1550

    PubMed  CAS  Google Scholar 

  • Kim SH, Turnbull J, Guimond S (2011) Extracellular matrix and cell signalling: the dynamic cooperation of integrin, proteoglycan and growth factor receptor. J Endocrinol 209:139–151

    PubMed  CAS  Google Scholar 

  • Krushel LA, Prieto AL, Edelman GM, Crossin KL (1994) Differential effects of cytotactin/tenascin fusion proteins on intracellular pH and cell morphology. J Cell Physiol 161:508–518

    PubMed  CAS  Google Scholar 

  • Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685

    PubMed  CAS  Google Scholar 

  • Lange K, Kammerer M, Saupe F, Hegi ME, Grotegut S, Fluri E, Orend G (2008) Combined lysophosphatidic acid/platelet-derived growth factor signaling triggers glioma cell migration in a tenascin-C microenvironment. Cancer Res 68:6942–6952

    PubMed  CAS  Google Scholar 

  • Latijnhouwers MA, Jongh GJ de, Bergers M, Rooij MJ de, Schalkwijk J (2000) Expression of tenascin-C splice variants by human skin cells. Arch Dermatol Res 292:446–454

    Google Scholar 

  • Lorger M, Krueger JS, O’Neal M, Staflin K, Felding-Habermann B (2009) Activation of tumor cell integrin alphavbeta3 controls angiogenesis and metastatic growth in the brain. Proc Natl Acad Sci U S A 106:10666–10671

    PubMed  CAS  Google Scholar 

  • Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109

    PubMed  Google Scholar 

  • Mackie EJ, Tucker RP (1992) Tenascin in bone morphogenesis: expression by osteoblasts and cell type-specific expression of splice variants. J Cell Sci 103:765–771

    PubMed  CAS  Google Scholar 

  • Marchisio PC, Bondanza S, Cremona O, Cancedda R, De Luca M (1991) Polarized expression of integrin receptors (alpha 6 beta 4, alpha 2 beta 1, alpha 3 beta 1, and alpha v beta 5) and their relationship with the cytoskeleton and basement membrane matrix in cultured human keratinocytes. J Cell Biol 112:761–773

    PubMed  CAS  Google Scholar 

  • Markovic DS, Vinnakota K, Chirasani S, Synowitz M, Raguet H, Stock K, Sliwa M, Lehmann S, Kalin R, Rooijen N van, Holmbeck K, Heppner FL, Kiwit J, Matyash V, Lehnardt S, Kaminska B, Glass R, Kettenmann H (2009) Gliomas induce and exploit microglial MT1-MMP expression for tumor expansion. Proc Natl Acad Sci U S A 106:12530–12535

    Google Scholar 

  • Maseruka H, Ridgway A, Tullo A, Bonshek R (2000) Developmental changes in patterns of expression of tenascin-C variants in the human cornea. Invest Ophthalmol Vis Sci 41:4101–4107

    PubMed  CAS  Google Scholar 

  • Merril CR, Goldman D, Sedman SA, Ebert MH (1981) Ultrasensitive stain for proteins in polyacrylamide gels shows regional variation in cerebrospinal fluid proteins. Science 211:1437–1438

    PubMed  CAS  Google Scholar 

  • Michele M, Faissner A (2009) Tenascin-C stimulates contactin-dependent neurite outgrowth via activation of phospholipase C. Mol Cell Neurosci 41:397–408

    PubMed  CAS  Google Scholar 

  • Midwood KS, Orend G (2009) The role of tenascin-C in tissue injury and tumorigenesis. J Cell Commun Signal 3:287–310

    PubMed  Google Scholar 

  • Midwood KS, Hussenet T, Langlois B, Orend G (2011) Advances in tenascin-C biology. Cell Mol Life Sci 68:3175–3199

    PubMed  CAS  Google Scholar 

  • Mighell AJ, Thompson J, Hume WJ, Markham AF, Robinson PA (1997) Human tenascin-C: identification of a novel type III repeat in oral cancer and of novel splice variants in normal, malignant and reactive oral mucosae. Int J Cancer 72:236–240

    PubMed  CAS  Google Scholar 

  • Murphy-Ullrich JE, Lightner VA, Aukhil I, Yan YZ, Erickson HP, Höök M (1991) Focal adhesion integrity is downregulated by the alternatively spliced domain of human tenascin. J Cell Biol 115:1127–1136

    PubMed  CAS  Google Scholar 

  • Nakamura-Ishizu A, Okuno Y, Omatsu Y, Okabe K, Morimoto J, Uede T, Nagasawa T, Suda T, Kubota Y (2012) Extracellular matrix protein tenascin-C is required in the bone marrow microenvironment primed for hematopoietic regeneration. Blood 119:5429–5437

    PubMed  CAS  Google Scholar 

  • Ohgaki H, Kleihues P (2005) Epidemiology and etiology of gliomas. Acta Neuropathol (Berl) 109:93–108

    Google Scholar 

  • Orend G (2005) Potential oncogenic action of tenascin-C in tumorigenesis. Int J Biochem Cell Biol 37:1066–1083

    PubMed  CAS  Google Scholar 

  • Orend G, Chiquet-Ehrismann R (2006) Tenascin-C induced signaling in cancer. Cancer Lett 244:143–163

    PubMed  CAS  Google Scholar 

  • Orlova VV, Liu Z, Goumans MJ, Dijke P ten (2011) Controlling angiogenesis by two unique TGF-beta type I receptor signaling pathways. Histol Histopathol 26:1219–1230

    Google Scholar 

  • Pawson T (1995) Protein modules and signalling networks. Nature 373:573–580

    PubMed  CAS  Google Scholar 

  • Pennock S, Wang Z (2003) Stimulation of cell proliferation by endosomal epidermal growth factor receptor as revealed through two distinct phases of signaling. Mol Cell Biol 23:5803–5815

    PubMed  CAS  Google Scholar 

  • Perou CM, Sorlie T, Eisen MB, Rijn M van de, Jeffrey SS, Rees CA, Pollack JR, Ross DT, Johnsen H, Akslen LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lonning PE, Borresen-Dale AL, Brown PO, Botstein D (2000) Molecular portraits of human breast tumours. Nature 406:747–752

    Google Scholar 

  • Pontén J, MacIntyre EH (1968) Long term culture of normal and neoplastic human glia. Acta Pathol Microbiol Scand 74:465–486

    PubMed  Google Scholar 

  • Pontén J, Westermark B (1978) Properties of human malignant glioma cells in vitro. Med Biol 56:184–193

    PubMed  Google Scholar 

  • Prieto AL, Edelman GM, Crossin KL (1993) Multiple integrins mediate cell attachment to cytotactin/tenascin. Proc Natl Acad Sci U S A 90:10154–10158

    PubMed  CAS  Google Scholar 

  • Riemenschneider MJ, Reifenberger G (2009) Molecular neuropathology of gliomas. Int J Mol Sci 10:184–212

    PubMed  CAS  Google Scholar 

  • Rozario T, Desimone DW (2009) The extracellular matrix in development and morphogenesis: a dynamic view. Dev Biol 341:126–140

    PubMed  Google Scholar 

  • Sahlberg C, Aukhil I, Thesleff I (2001) Tenascin-C in developing mouse teeth: expression of splice variants and stimulation by TGFbeta and FGF. Eur J Oral Sci 109:114–124

    PubMed  CAS  Google Scholar 

  • Saito Y, Shiota Y, Nishisaka M, Owaki T, Shimamura M, Fukai F (2008) Inhibition of angiogenesis by a tenascin-c peptide which is capable of activating beta1-integrins. Biol Pharm Bull 31:1003–1007

    PubMed  CAS  Google Scholar 

  • Sarkar S, Nuttall RK, Liu S, Edwards DR, Yong VW (2006) Tenascin-C stimulates glioma cell invasion through matrix metalloproteinase-12. Cancer Res 66:11771–11780

    PubMed  CAS  Google Scholar 

  • Sasaki T, Fassler R, Hohenester E (2004) Laminin: the crux of basement membrane assembly. J Cell Biol 164:959–963

    PubMed  CAS  Google Scholar 

  • Schachtrup C, Ryu JK, Helmrick MJ, Vagena E, Galanakis DK, Degen JL, Margolis RU, Akassoglou K (2010) Fibrinogen triggers astrocyte scar formation by promoting the availability of active TGF-beta after vascular damage. J Neurosci 30:5843–5854

    PubMed  CAS  Google Scholar 

  • Schneider MR, Wolf E (2009) The epidermal growth factor receptor ligands at a glance. J Cell Physiol 218:460–466

    PubMed  CAS  Google Scholar 

  • Scholze A, Gotz B, Faissner A (1996) Glial cell interactions with tenascin-C: adhesion and repulsion to different tenascin-C domains is cell type related. Int J Dev Neurosci 14:315–329

    PubMed  CAS  Google Scholar 

  • Schultz GS, Wysocki A (2009) Interactions between extracellular matrix and growth factors in wound healing. Wound Repair Regen 17:153–162

    PubMed  Google Scholar 

  • Seiffert M, Beck SC, Schermutzki F, Muller CA, Erickson HP, Klein G (1998) Mitogenic and adhesive effects of tenascin-C on human hematopoietic cells are mediated by various functional domains. Matrix Biol 17:47–63

    PubMed  CAS  Google Scholar 

  • Sevier CS, Kaiser CA (2002) Formation and transfer of disulphide bonds in living cells. Nat Rev Mol Cell Biol 3:836–847

    PubMed  CAS  Google Scholar 

  • Shaw LM (1999) Integrin function in breast carcinoma progression. J Mammary Gland Biol Neoplasia 4:367–376

    PubMed  CAS  Google Scholar 

  • Silacci M, Brack SS, Spath N, Buck A, Hillinger S, Arni S, Weder W, Zardi L, Neri D (2006) Human monoclonal antibodies to domain C of tenascin-C selectively target solid tumors in vivo. Protein Eng Des Sel 19:471–478

    PubMed  CAS  Google Scholar 

  • Silver DJ, Steindler DA (2009) Common astrocytic programs during brain development, injury and cancer. Trends Neurosci 32:303–311

    PubMed  CAS  Google Scholar 

  • Soung YH, Gil HJ, Clifford JL, Chung J (2011) Role of alpha6beta4 integrin in cell motility, invasion and metastasis of mammary tumors. Curr Protein Pept Sci 12:23–29

    PubMed  CAS  Google Scholar 

  • Sriramarao P, Mendler M, Bourdon MA (1993) Endothelial cell attachment and spreading on human tenascin is mediated by a2b1 and avb3 integrins. J Cell Sci 105:1001–1012

    PubMed  CAS  Google Scholar 

  • Swindle CS, Tran KT, Johnson TD, Banerjee P, Mayes AM, Griffith L, Wells A (2001) Epidermal growth factor (EGF)-like repeats of human tenascin-C as ligands for EGF receptor. J Cell Biol 154:459–468

    PubMed  CAS  Google Scholar 

  • Tanaka M, Yamazaki T, Araki N, Yoshikawa H, Yoshida T, Sakakura T, Uchida A (2000) Clinical significance of tenascin-C expression in osteosarcoma: tenascin-C promotes distant metastases of osteosarcoma. Int J Mol Med 5:505–510

    PubMed  CAS  Google Scholar 

  • Trebaul A, Chan EK, Midwood KS (2007) Regulation of fibroblast migration by tenascin-C. Biochem Soc Trans 35:695–697

    PubMed  CAS  Google Scholar 

  • Tremble P, Chiquet-Ehrismann R, Werb Z (1994) The extracellular matrix ligands fibronectin and tenascin collaborate in regulating collagenase gene expression in fibroblasts. Mol Biol Cell 5:439–453

    PubMed  CAS  Google Scholar 

  • Tsunoda T, Inada H, Kalembeyi I, Imanaka-Yoshida K, Sakakibara M, Okada R, Katsuta K, Sakakura T, Majima Y, Yoshida T (2003) Involvement of large tenascin-C splice variants in breast cancer progression. Am J Pathol 162:1857–1867

    PubMed  CAS  Google Scholar 

  • Uhm JH, Gladson CL, Rao JS (1999) The role of integrins in the malignant phenotype of gliomas. Front Biosci 4:D188–D199

    PubMed  CAS  Google Scholar 

  • Van Obberghen-Schilling E, Tucker RP, Saupe F, Gasser I, Cseh B, Orend G (2011) Fibronectin and tenascin-C: accomplices in vascular morphogenesis during development and tumor growth. Int J Dev Biol 55:511–525

    PubMed  Google Scholar 

  • Vollmer G, Tan MI, Wunsche W, Frank K (1997) Expression of tenascin-C by human endometrial adenocarcinoma and stroma cells: heterogeneity of splice variants and induction by TGF-beta. Biochem Cell Biol 75:759–769

    PubMed  CAS  Google Scholar 

  • von Holst A (2008) Tenascin C in stem cell niches: redundant, permissive or instructive? Cells Tissues Organs 188:170–177

    Google Scholar 

  • Wang H, Leavitt L, Ramaswamy R, Rapraeger AC (2010) Interaction of syndecan and alpha6beta4 integrin cytoplasmic domains: regulation of ErbB2-mediated integrin activation. J Biol Chem 285:13569–13579

    PubMed  CAS  Google Scholar 

  • Williams CM, Engler AJ, Slone RD, Galante LL, Schwarzbauer JE (2008) Fibronectin expression modulates mammary epithelial cell proliferation during acinar differentiation. Cancer Res 68:3185–3192

    PubMed  CAS  Google Scholar 

  • Williams SA, Schwarzbauer JE (2009) A shared mechanism of adhesion modulation for tenascin-C and fibulin-1. Mol Biol Cell 20:1141–1149

    PubMed  CAS  Google Scholar 

  • Wilson KE, Bartlett JM, Miller EP, Smyth JF, Mullen P, Miller WR, Langdon SP (1999) Regulation and function of the extracellular matrix protein tenascin-C in ovarian cancer cell lines. Br J Cancer 80:685–692

    PubMed  CAS  Google Scholar 

  • Wong GS, Rustgi AK (2013) Matricellular proteins: priming the tumour microenvironment for cancer development and metastasis. Br J Cancer 108:755–761

    PubMed  CAS  Google Scholar 

  • Worth DC, Parsons M (2008) Adhesion dynamics: mechanisms and measurements. Int J Biochem Cell Biol 40:2397–2409

    PubMed  CAS  Google Scholar 

  • Yang Y, Dang D, Mogi S, Ramos DM (2004) Tenascin-C deposition requires beta3 integrin and Src. Biochem Biophys Res Commun 322:935–942

    PubMed  CAS  Google Scholar 

  • Yoshida T, Yoshimura E, Numata H, Sakakura Y, Sakakura T (1999) Involvement of tenascin-C in proliferation and migration of laryngeal carcinoma cells. Virchows Arch 435:496–500

    PubMed  CAS  Google Scholar 

  • Zalutsky MR, Reardon DA, Akabani G, Coleman RE, Friedman AH, Friedman HS, McLendon RE, Wong TZ, Bigner DD (2008) Clinical experience with alpha-particle emitting 211At: treatment of recurrent brain tumor patients with 211At-labeled chimeric antitenascin monoclonal antibody 81C6. J Nucl Med 49:30–38

    PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Prof. Dr. Harold P. Erickson (Department of Cell Biology, Duke University Medical Center, Durham, N.C., USA) for the gift of expression plasmids corresponding to human TN-C domains and for purified TNfbg- and TNegf-proteins. We are grateful to Dr. W. Mütze for preparing single-domain expression plasmids.

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Author notes

  1. Frank K. H. van Landeghem

    Present address: Department of Laboratory Medicine and Pathology, 5B4.17 Walter Mackenzie Health Sciences Centre, University of Alberta, Edmonton, Alberta, Canada

Authors and Affiliations

  1. Department of Cell Morphology and Molecular Neurobiology, Ruhr University Bochum, Bochum, Germany

    Nicole Brösicke & Andreas Faissner

  2. Institute of Neuropathology and Reference Center for Brain Tumors (DGNN), University of Bonn Medical Center, Bonn, Germany

    Frank K. H. van Landeghem

  3. Institute for Reconstructive Neurobiology, LIFE and Brain, University of Bonn, Bonn, Germany

    Björn Scheffler

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  4. Andreas Faissner
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Correspondence to Andreas Faissner.

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B.S. was supported by the Lichtenberg program of the VW foundation.

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Supplemental figure 1

Tenascin-C fragments (TNfns) of the alternatively spliced region were expressed for use in epitope mapping. Based on the intact TN-C molecule a, we chose the desired alternatively spliced domains b. Primers were generated and the individual annealing temperature was established c. All of the recombinantly expressed domains of the alternatively spliced region showed specific reaction in Western blots with the polyclonal anti-TN-C antibody d (JPEG 21 kb)

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Supplemental figure 2

Fractions of the sequential expression steps for the various TN-C fragments. a TNfn1-5. b TNfn3-5. c TNfn6-8. d TNfnALL. Lanes show fractions: noninduced control, induced control, bacterial supernatant and pellet. Relative molecular mass in kDa is indicated left (JPEG 55 kb)

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Supplemental figure 3

TNfns were successfully purified by using various chromatographic systems. After expression of the TNfns and harvest of the bacterial cells, various forms of chromatography were performed to purify the proteins. Top Time flow of purification steps. a TNfn 1–5 and TNfn3-5 were purified by using comparable chromatography techniques. b, c The recombinantly expressed proteins were produced in large amounts as shown by Coomassie-stained 10 % acylamide gels after ion exchange (left). The specificity was determined by Western blot with polyclonal anti-TN-C antibody after ion exchange (middle). Heparin-Sepharose chromatography yields protein fragments of the highest purity. d For purification of TNfn6-8, only ion-exchange chromatography gave highly purified TNfn6-8. Left Coomassie staining of 12 % SDS gel after ion exchange. Right Corresponding Western blot with the polyclonal TN-C antibody. e The longest protocol for purification was needed for TNfnALL. Gel filtration via a sephacryl column (left Coomassie-stained SDS gel) is followed by an ion-exchange step (middle Coomassie-stained SDS gel). The TN-C specificity could again be determined by using the polyclonal TN-C antibody (JPEG 60 kb)

High resolution (TIFF 4860 kb)

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Brösicke, N., van Landeghem, F.K.H., Scheffler, B. et al. Tenascin-C is expressed by human glioma in vivo and shows a strong association with tumor blood vessels. Cell Tissue Res 354, 409–430 (2013). https://doi.org/10.1007/s00441-013-1704-9

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