Cancer and Metastasis Reviews

, Volume 29, Issue 4, pp 595–606

Expression of tenascin-C and its isoforms in the breast



Tenascin-C (TNC) is an extracellular matrix glycoprotein which is frequently up-regulated in a variety of pathological conditions including chronic inflammation and cancer. TNC has been implicated in the modulation of cell migration, proliferation, invasion and angiogenesis. Multiple isoforms of TNC can be generated through the alternative splicing of nine exons located in the fibronectin type III region of the molecule. The profile of isoforms expressed differs between cancers and normal breast, with the fully truncated TNC isoform being predominant in normal and benign tissues and higher molecular weight isoforms induced predominantly in cancer. The addition of extra domains within the fibronectin type III repeat domain greatly affects TNC function with multiple exon combinations available for splicing. Exons 14 and 16 are considered to be tumour-associated and have been shown to affect breast cell line invasion and growth in vitro to a greater extent than the full-length TNC isoform. This mini review will provide a summary of the literature to date regarding the expression of TNC isoforms in the breast and also discuss more recent developments in the field regarding exon AD1.


Tenascin-C TNC isoforms Breast cancer Extracellular matrix 



Additional domain


Ductal carcinoma in situ


Extracellular matrix


Epidermal growth factor-like


Epithelial–mesenchymal transition


Oestrogen receptor


Extracellular signal-regulated kinase






In situ hybridisation


Mitogen-activated protein kinase


Metastasis-free survival


Matrix metalloproteinase


N-methyl nitrosourea


Non-small cell lung cancer


Progression-free survival


Post-relapse survival


S-phase fraction


Transforming growth factor beta




Tenascin-C with only exon 16 of variable region


Tenascin-C with only exons 14 and 16 of variable region


Tenascin-C with exons 14, AD1 and 16 of variable region


Full-length tenascin-C splice variant


Fully truncated tenascin-C


  1. 1.
    Bissell, M. J., & Radisky, D. (2001). Putting tumours in context. Nature Reviews Cancer, 1, 46–54.PubMedGoogle Scholar
  2. 2.
    Liotta, L. A., & Kohn, E. C. (2001). The microenvironment of the tumour–host interface. Nature, 411, 375–379.PubMedGoogle Scholar
  3. 3.
    de Visser, K. E., & Coussens, L. M. (2006). The inflammatory tumor microenvironment and its impact on cancer development. Contributions to Microbiology, 13, 118–137.PubMedGoogle Scholar
  4. 4.
    Egeblad, M., Littlepage, L. E., & Werb, Z. (2005). The fibroblastic coconspirator in cancer progression. Cold Spring Harbor Symposia on Quantative Biology, 70, 383–388.Google Scholar
  5. 5.
    Ma, X. J., Dahiya, S., Richardson, E., Erlander, M., & Sgroi, D. C. (2009). Gene expression profiling of the tumor microenvironment during breast cancer progression. Breast Cancer Research, 11, R7.PubMedGoogle Scholar
  6. 6.
    Kalluri, R., & Zeisberg, M. (2006). Fibroblasts in cancer. Nature Reviews Cancer, 6, 392–401.PubMedGoogle Scholar
  7. 7.
    Carnemolla, B., Castellani, P., Ponassi, M., Borsi, L., Urbini, S., Nicolo, G., et al. (1999). Identification of a glioblastoma-associated tenascin-C isoform by a high affinity recombinant antibody. American Journal of Pathology, 154, 1345–1352.PubMedGoogle Scholar
  8. 8.
    Fuss, B., Pott, U., Fischer, P., Schwab, M. E., & Schachner, M. (1991). Identification of a cDNA clone specific for the oligodendrocyte-derived repulsive extracellular matrix molecule J1-160/180. Journal of Neuroscience Research, 29, 299–307.PubMedGoogle Scholar
  9. 9.
    Weber, P., Montag, D., Schachner, M., & Bernhardt, R. R. (1998). Zebrafish tenascin-W, a new member of the tenascin family. Journal of Neurobiology, 35, 1–16.PubMedGoogle Scholar
  10. 10.
    Scherberich, A., Tucker, R. P., Degen, M., Brown-Luedi, M., Andres, A. C., & Chiquet-Ehrismann, R. (2005). Tenascin-W is found in malignant mammary tumors, promotes alpha8 integrin-dependent motility and requires p38MAPK activity for BMP-2 and TNF-alpha induced expression in vitro. Oncogene, 24, 1525–1532.PubMedGoogle Scholar
  11. 11.
    Degen, M., Brellier, F., Kain, R., Ruiz, C., Terracciano, L., Orend, G., et al. (2007). Tenascin-W is a novel marker for activated tumor stroma in low-grade human breast cancer and influences cell behavior. Cancer Research, 67, 9169–9179.PubMedGoogle Scholar
  12. 12.
    Bristow, J., Tee, M. K., Gitelman, S. E., Mellon, S. H., & Miller, W. L. (1993). Tenascin-X: a novel extracellular matrix protein encoded by the human XB gene overlapping P450c21B. Journal of Cell Biology, 122, 265–278.PubMedGoogle Scholar
  13. 13.
    Mao, J. R., Taylor, G., Dean, W. B., Wagner, D. R., Afzal, V., Lotz, J. C., et al. (2002). Tenascin-X deficiency mimics Ehlers–Danlos syndrome in mice through alteration of collagen deposition. Nature Genetics, 30, 421–425.PubMedGoogle Scholar
  14. 14.
    Burch, G. H., Gong, Y., Liu, W., Dettman, R. W., Curry, C. J., Smith, L., et al. (1997). Tenascin-X deficiency is associated with Ehlers–Danlos syndrome. Nature Genetics, 17, 104–108.PubMedGoogle Scholar
  15. 15.
    Hagios, C., Koch, M., Spring, J., Chiquet, M., & Chiquet-Ehrismann, R. (1996). Tenascin-Y: A protein of novel domain structure is secreted by differentiated fibroblasts of muscle connective tissue. Journal of Cell Biology, 134, 1499–1512.PubMedGoogle Scholar
  16. 16.
    Chiquet-Ehrismann, R. (2004). Tenascins. International Journal of Biochemistry & Cell Biology, 36, 986–990.Google Scholar
  17. 17.
    Chiquet-Ehrismann, R., & Chiquet, M. (2003). Tenascins: Regulation and putative functions during pathological stress. Journal of Pathology, 200, 488–499.PubMedGoogle Scholar
  18. 18.
    Hsia, H. C., & Schwarzbauer, J. E. (2005). Meet the tenascins: Multifunctional and mysterious. Journal of Biological Chemistry, 280, 26641–26644.PubMedGoogle Scholar
  19. 19.
    Chung, C. Y., Murphy-Ullrich, J. E., & Erickson, H. P. (1996). Mitogenesis, cell migration, and loss of focal adhesions induced by tenascin-C interacting with its cell surface receptor, annexin II. Molecular Biology of the Cell, 7, 883–892.PubMedGoogle Scholar
  20. 20.
    Ghert, M. A., Qi, W. N., Erickson, H. P., Block, J. A., & Scully, S. P. (2001). Tenascin-C splice variant adhesive/anti-adhesive effects on chondrosarcoma cell attachment to fibronectin. Cell Structure and Function, 26, 179–187.PubMedGoogle Scholar
  21. 21.
    Midwood, K. S., & Orend, G. (2009). The role of tenascin-C in tissue injury and tumorigenesis. Journal of Cell Communication and Signaling, 3, 287–310.PubMedGoogle Scholar
  22. 22.
    Jones, P. L., & Jones, F. S. (2000). Tenascin-C in development and disease: Gene regulation and cell function. Matrix Biology, 19, 581–596.PubMedGoogle Scholar
  23. 23.
    Jones, F. S., & Jones, P. L. (2000). The tenascin family of ECM glycoproteins: Structure, function, and regulation during embryonic development and tissue remodeling. Developmental Dynamics, 218, 235–259.PubMedGoogle Scholar
  24. 24.
    Erickson, H. P., & Inglesias, J. L. (1984). A six-armed oligomer isolated from cell surface fibronectin preparations. Nature, 311, 267–269.PubMedGoogle Scholar
  25. 25.
    Hancox, R. A., Allen, M. D., Holliday, D. L., Edwards, D. R., Pennington, C. J., Guttery, D. S., et al. (2009). Tumour-associated tenascin-C isoforms promote breast cancer cell invasion and growth by matrix metalloproteinase-dependent and independent mechanisms. Breast Cancer Research, 11, R24.PubMedGoogle Scholar
  26. 26.
    Orend, G., & Chiquet-Ehrismann, R. (2006). Tenascin-C induced signaling in cancer. Cancer Letters, 244, 143–163.PubMedGoogle Scholar
  27. 27.
    Howeedy, A. A., Virtanen, I., Laitinen, L., Gould, N. S., Koukoulis, G. K., & Gould, V. E. (1990). Differential distribution of tenascin in the normal, hyperplastic, and neoplastic breast. Laboratory Investigation, 63, 798–806.PubMedGoogle Scholar
  28. 28.
    Jahkola, T., Toivonen, T., Virtanen, I., von Smitten, K., Nordling, S., von Boguslawski, K., et al. (1998). Tenascin-C expression in invasion border of early breast cancer: A predictor of local and distant recurrence. British Journal of Cancer, 78, 1507–1513.PubMedGoogle Scholar
  29. 29.
    Adams, M., Jones, J. L., Walker, R. A., Pringle, J. H., & Bell, S. C. (2002). Changes in tenascin-C isoform expression in invasive and preinvasive breast disease. Cancer Research, 62, 3289–3297.PubMedGoogle Scholar
  30. 30.
    Murphy-Ullrich, J. E., Lightner, V. A., Aukhil, I., Yan, Y. Z., Erickson, H. P., & Hook, M. (1991). Focal adhesion integrity is downregulated by the alternatively spliced domain of human tenascin. Journal of Cell Biology, 115, 1127–1136.PubMedGoogle Scholar
  31. 31.
    Phillips, G. R., Krushel, L. A., & Crossin, K. L. (1998). Domains of tenascin involved in glioma migration. Journal of Cell Science, 111(Pt 8), 1095–1104.PubMedGoogle Scholar
  32. 32.
    Taraseviciute, A., Vincent, B. T., Schedin, P., & Jones, P. L. (2010). Quantitative analysis of three-dimensional human mammary epithelial tissue architecture reveals a role for tenascin-C in regulating c-met function. American Journal of Pathology, 176, 827–838.PubMedGoogle Scholar
  33. 33.
    Chiquet-Ehrismann, R., Mackie, E. J., Pearson, C. A., & Sakakura, T. (1986). Tenascin: An extracellular matrix protein involved in tissue interactions during fetal development and oncogenesis. Cell, 47, 131–139.PubMedGoogle Scholar
  34. 34.
    Russo, J., & Russo, I. H. (1996). Experimentally induced mammary tumors in rats. Breast Cancer Research and Treatment, 39, 7–20.PubMedGoogle Scholar
  35. 35.
    Tsubura, A., Yoshizawa, K., Uehara, N., Yuri, T., & Matsuoka, Y. (2007). Multistep mouse mammary tumorigenesis through pre-neoplasia to neoplasia and acquisition of metastatic potential. Medical Molecular Morphology, 40, 9–17.PubMedGoogle Scholar
  36. 36.
    Mackie, E. J., Chiquet-Ehrismann, R., Adams Pearson, C., Inaguma, Y., Taya, K., Kawarada, Y., et al. (1987). Tenascin is a stromal marker for epithelial malignancy in the mammary gland. Proceedings of the National Academy of Sciences U S A, 84, 4621–4625.Google Scholar
  37. 37.
    Inaguma, Y., Kusakabe, M., Mackie, E. J., Pearson, C. A., Chiquet-Ehrismann, R., & Sakakura, T. (1988). Epithelial induction of stromal tenascin in the mouse mammary gland: From embryogenesis to carcinogenesis. Developmental Biology, 128, 245–255.PubMedGoogle Scholar
  38. 38.
    Bell, S. C., Pringle, J. H., Taylor, D. J., & Malak, T. M. (1999). Alternatively spliced tenascin-C mRNA isoforms in human fetal membranes. Molecular Human Reproduction, 5, 1066–1076.PubMedGoogle Scholar
  39. 39.
    Erickson, H. P., & Bourdon, M. A. (1989). Tenascin: An extracellular matrix protein prominent in specialized embryonic tissues and tumors. Annual Review of Cell Biology, 5, 71–92.PubMedGoogle Scholar
  40. 40.
    Erickson, H. P., & Lightner, V. A. (1988). Hexabrachion protein (tenascin, cytotactin, brachionectin) in connective tissues, embryonic brain, and tumors. Advanced Cell Biology, 2, 55–90.Google Scholar
  41. 41.
    Chiquet-Ehrismann, R., Kalla, P., & Pearson, C. A. (1989). Participation of tenascin and transforming growth factor-beta in reciprocal epithelial–mesenchymal interactions of MCF7 cells and fibroblasts. Cancer Research, 49, 4322–4325.PubMedGoogle Scholar
  42. 42.
    Maschler, S., Grunert, S., Danielopol, A., Beug, H., & Wirl, G. (2004). Enhanced tenascin-C expression and matrix deposition during Ras/TGF-beta-induced progression of mammary tumor cells. Oncogene, 23, 3622–3633.PubMedGoogle Scholar
  43. 43.
    Kawakatsu, H., Shiurba, R., Obara, M., Hiraiwa, H., Kusakabe, M., & Sakakura, T. (1992). Human carcinoma cells synthesize and secrete tenascin in vitro. Japanese Journal of Cancer Research, 83, 1073–1080.PubMedGoogle Scholar
  44. 44.
    Lightner, V. A., Marks, J. R., & McCachren, S. S. (1994). Epithelial cells are an important source of tenascin in normal and malignant human breast tissue. Experimental Cell Research, 210, 177–184.PubMedGoogle Scholar
  45. 45.
    Dandachi, N., Hauser-Kronberger, C., More, E., Wiesener, B., Hacker, G. W., Dietze, O., et al. (2001). Co-expression of tenascin-C and vimentin in human breast cancer cells indicates phenotypic transdifferentiation during tumour progression: Correlation with histopathological parameters, hormone receptors, and oncoproteins. Journal of Pathology, 193, 181–189.PubMedGoogle Scholar
  46. 46.
    Gordon, L. A., Mulligan, K. T., Maxwell-Jones, H., Adams, M., Walker, R. A., & Jones, J. L. (2003). Breast cell invasive potential relates to the myoepithelial phenotype. International Journal of Cancer, 106, 8–16.Google Scholar
  47. 47.
    Jahkola, T., Toivonen, T., von Smitten, K., Blomqvist, C., & Virtanen, I. (1996). Expression of Tenascin in invasion border of early breast cancer correlates with higher risk of distant metastasis. International Journal of Cancer, 69, 445–447.Google Scholar
  48. 48.
    Jahkola, T. (1998). Self-perceptions of women after early breast cancer surgery. European Journal of Surgical Oncology, 24, 9–14.PubMedGoogle Scholar
  49. 49.
    Shoji, T., Kamiya, T., Tsubura, A., Hatano, T., Sakakura, T., Yamamoto, M., et al. (1992). Immunohistochemical staining patterns of tenascin in invasive breast carcinomas. Virchows Archiv. A, Pathological Anatomy and Histopathology, 421, 53–56.PubMedGoogle Scholar
  50. 50.
    Ferguson, J. E., Schor, A. M., Howell, A., & Ferguson, M. W. (1990). Tenascin distribution in the normal human breast is altered during the menstrual cycle and in carcinoma. Differentiation, 42, 199–207.PubMedGoogle Scholar
  51. 51.
    Vollmer, G., Siegal, G. P., Chiquet-Ehrismann, R., Lightner, V. A., Arnholdt, H., & Knuppen, R. (1990). Tenascin expression in the human endometrium and in endometrial adenocarcinomas. Laboratory Investigation, 62, 725–730.PubMedGoogle Scholar
  52. 52.
    Jahkola, T., Toivonen, T., Nordling, S., von Smitten, K., & Virtanen, I. (1998). Expression of tenascin-C in intraductal carcinoma of human breast: Relationship to invasion. European Journal of Cancer, 34, 1687–1692.PubMedGoogle Scholar
  53. 53.
    Goepel, C., Buchmann, J., Schultka, R., & Koelbl, H. (2000). Tenascin-A marker for the malignant potential of preinvasive breast cancers. Gynecologic Oncology, 79, 372–378.PubMedGoogle Scholar
  54. 54.
    Tokes, A. M., Paku, S., Toth, S., Paal, E., Kulka, J., Toth, J., et al. (2000). Tenascin expression in primary and recurrent breast carcinomas and the effect of tenascin on breast tumor cell cultures. Pathology and Oncology Research, 6, 202–209.PubMedGoogle Scholar
  55. 55.
    Gould, V. E., Koukoulis, G. K., & Virtanen, I. (1990). Extracellular matrix proteins and their receptors in the normal, hyperplastic and neoplastic breast. Cell Differentiation and Development, 32, 409–416.PubMedGoogle Scholar
  56. 56.
    Koukoulis, G. K., Gould, V. E., Bhattacharyya, A., Gould, J. E., Howeedy, A. A., & Virtanen, I. (1991). Tenascin in normal, reactive, hyperplastic, and neoplastic tissues: Biologic and pathologic implications. Human Pathology, 22, 636–643.PubMedGoogle Scholar
  57. 57.
    Moch, H., Torhorst, J., Durmuller, U., Feichter, G. E., Sauter, G., & Gudat, F. (1993). Comparative analysis of the expression of tenascin and established prognostic factors in human breast cancer. Pathology, Research and Practice, 189, 510–514.PubMedGoogle Scholar
  58. 58.
    Natali, P. G., Nicotra, M. R., Bigotti, A., Botti, C., Castellani, P., Risso, A. M., et al. (1991). Comparative analysis of the expression of the extracellular matrix protein tenascin in normal human fetal, adult and tumor tissues. International Journal of Cancer, 47, 811–816.Google Scholar
  59. 59.
    Shrestha, P., Sakamoto, F., Takagi, H., Yamada, T., & Mori, M. (1994). Enhanced tenascin immunoreactivity in leukoplakia and squamous cell carcinoma of the oral cavity: An immunohistochemical study. European Journal of Cancer Part B: Oral Oncology, 30B, 132–137.Google Scholar
  60. 60.
    Shrestha, P., Sumitomo, S., Ogata, K., Yamada, K., Takai, Y., Yang, L., et al. (1994). Immunoreactive tenascin in tumours of salivary glands: Evidence for enhanced expression in tumour stroma and production by tumour cells. European Journal of Cancer Part B: Oral Oncology, 30B, 393–399.Google Scholar
  61. 61.
    Yamanaka, M., Taga, M., & Minaguchi, H. (1996). Immunohistological localization of tenascin in the human endometrium. Gynecologic and Obstetric Investigation, 41, 247–252.PubMedGoogle Scholar
  62. 62.
    Weigelt, B., Peterse, J. L., & van’t Veer, L. J. (2005). Breast cancer metastasis: Markers and models. Nature Reviews Cancer, 5, 591–602.PubMedGoogle Scholar
  63. 63.
    Joyce, J. A., & Pollard, J. W. (2009). Microenvironmental regulation of metastasis. Nature Reviews Cancer, 9, 239–252.PubMedGoogle Scholar
  64. 64.
    Tsunoda, T., Inada, H., Kalembeyi, I., Imanaka-Yoshida, K., Sakakibara, M., Okada, R., et al. (2003). Involvement of large tenascin-C splice variants in breast cancer progression. American Journal of Pathology, 162, 1857–1867.PubMedGoogle Scholar
  65. 65.
    Emoto, K., Yamada, Y., Sawada, H., Fujimoto, H., Ueno, M., Takayama, T., et al. (2001). Annexin II overexpression correlates with stromal tenascin-C overexpression: A prognostic marker in colorectal carcinoma. Cancer, 92, 1419–1426.PubMedGoogle Scholar
  66. 66.
    Kusagawa, H., Onoda, K., Namikawa, S., Yada, I., Okada, A., Yoshida, T., et al. (1998). Expression and degeneration of tenascin-C in human lung cancers. British Journal of Cancer, 77, 98–102.PubMedGoogle Scholar
  67. 67.
    Leins, A., Riva, P., Lindstedt, R., Davidoff, M. S., Mehraein, P., & Weis, S. (2003). Expression of tenascin-C in various human brain tumors and its relevance for survival in patients with astrocytoma. Cancer, 98, 2430–2439.PubMedGoogle Scholar
  68. 68.
    Ioachim, E., Charchanti, A., Briasoulis, E., Karavasilis, V., Tsanou, H., Arvanitis, D. L., et al. (2002). Immunohistochemical expression of extracellular matrix components tenascin, fibronectin, collagen type IV and laminin in breast cancer: Their prognostic value and role in tumour invasion and progression. European Journal of Cancer, 38, 2362–2370.PubMedGoogle Scholar
  69. 69.
    Thiery, J. P. (2002). Epithelial–mesenchymal transitions in tumour progression. Nature Reviews Cancer, 2, 442–454.PubMedGoogle Scholar
  70. 70.
    Tavazoie, S. F., Alarcón, C., Oskarsson, T., Padua, D., Wang, Q., Bos, P. D., et al. (2008). Endogenous human microRNAs that suppress breast cancer metastasis. Nature, 451, 147–152.PubMedGoogle Scholar
  71. 71.
    Sugawara, I., Hirakoshi, J., Masunaga, A., Itoyama, S., & Sakakura, T. (1991). Reduced tenascin expression in colonic carcinoma with lymphogenous metastasis. Invasion and Metastasis, 11, 325–331.Google Scholar
  72. 72.
    Shoji, T., Kamiya, T., Tsubura, A., Hamada, Y., Hatano, T., Hioki, K., et al. (1993). Tenascin staining positivity and the survival of patients with invasive breast carcinoma. Journal of Surgical Research, 55, 295–297.PubMedGoogle Scholar
  73. 73.
    Ishihara, A., Yoshida, T., Tamaki, H., & Sakakura, T. (1995). Tenascin expression in cancer cells and stroma of human breast cancer and its prognostic significance. Clinical Cancer Research, 1, 1035–1041.PubMedGoogle Scholar
  74. 74.
    Tiitta, O., Wahlstrom, T., Paavonen, J., Linnala, A., Sharma, S., Gould, V. E., et al. (1992). Enhanced tenascin expression in cervical and vulvar koilocytotic lesions. American Journal of Pathology, 141, 907–913.PubMedGoogle Scholar
  75. 75.
    Helleman, J., Jansen, M. P., Ruigrok-Ritstier, K., van Staveren, I. L., Look, M. P., Meijer-van Gelder, M. E., et al. (2008). Association of an extracellular matrix gene cluster with breast cancer prognosis and endocrine therapy response. Clinical Cancer Research, 14, 5555–5564.PubMedGoogle Scholar
  76. 76.
    Joester, A., & Faissner, A. (1999). Evidence for combinatorial variability of tenascin-C isoforms and developmental regulation in the mouse central nervous system. Journal of Biological Chemistry, 274, 17144–17151.PubMedGoogle Scholar
  77. 77.
    von Holst, A., Egbers, U., Prochiantz, A., & Faissner, A. (2007). Neural stem/progenitor cells express 20 tenascin C isoforms that are differentially regulated by Pax6. Journal of Biological Chemistry, 282, 9172–9181.Google Scholar
  78. 78.
    Dorries, U., & Schachner, M. (1994). Tenascin mRNA isoforms in the developing mouse brain. Journal of Neuroscience Research, 37, 336–347.PubMedGoogle Scholar
  79. 79.
    Chiquet-Ehrismann, R., Matsuoka, Y., Hofer, U., Spring, J., Bernasconi, C., & Chiquet, M. (1991). Tenascin variants: Differential binding to fibronectin and distinct distribution in cell cultures and tissues. Cell Regulation, 2, 927–938.PubMedGoogle Scholar
  80. 80.
    Kaplony, A., Zimmermann, D. R., Fischer, R. W., Imhof, B. A., Odermatt, B. F., Winterhalter, K. H., et al. (1991). Tenascin Mr 220000 isoform expression correlates with corneal cell migration. Development, 112, 605–614.PubMedGoogle Scholar
  81. 81.
    Prieto, A. L., Jones, F. S., Cunningham, B. A., Crossin, K. L., & Edelman, G. M. (1990). Localization during development of alternatively spliced forms of cytotactin mRNA by in situ hybridization. Journal of Cell Biology, 111, 685–698.PubMedGoogle Scholar
  82. 82.
    Tucker, R. P. (1991). The sequential expression of tenascin mRNA in epithelium and mesenchyme during feather morphogenesis. Roux’s Archives of Developmental Biology, 200, 108–112.Google Scholar
  83. 83.
    Weller, A., Beck, S., & Ekblom, P. (1991). Amino acid sequence of mouse tenascin and differential expression of two tenascin isoforms during embryogenesis. Journal of Cell Biology, 112, 355–362.PubMedGoogle Scholar
  84. 84.
    Joester, A., & Faissner, A. (2001). The structure and function of tenascins in the nervous system. Matrix Biology, 20, 13–22.PubMedGoogle Scholar
  85. 85.
    Borsi, L., Balza, E., Castellani, P., Carnemolla, B., Ponassi, M., Querze, G., et al. (1994). Cell-cycle dependent alternative splicing of the tenascin primary transcript. Cell Adhesion and Communication, 1, 307–317.PubMedGoogle Scholar
  86. 86.
    Borsi, L., Allemanni, G., Gaggero, B., & Zardi, L. (1996). Extracellular pH controls pre-mRNA alternative splicing of tenascin-C in normal, but not in malignantly transformed, cells. International Journal of Cancer, 66, 632–635.Google Scholar
  87. 87.
    Vollmer, G., Tan, M. I., 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. Biochemistry and Cell Biology, 75, 759–769.PubMedGoogle Scholar
  88. 88.
    Chung, C. Y., & Erickson, H. P. (1994). Cell surface annexin II is a high affinity receptor for the alternatively spliced segment of tenascin-C. Journal of Cell Biology, 126, 539–548.PubMedGoogle Scholar
  89. 89.
    Huang, W., Chiquet-Ehrismann, R., Moyano, J. V., Garcia-Pardo, A., & Orend, G. (2001). Interference of tenascin-C with syndecan-4 binding to fibronectin blocks cell adhesion and stimulates tumor cell proliferation. Cancer Research, 61, 8586–8594.PubMedGoogle Scholar
  90. 90.
    Lange, K., Kammerer, M., Saupe, F., Hegi, M. E., Grotegut, S., Fluri, E., et al. (2008). Combined lysophosphatidic acid/platelet-derived growth factor signaling triggers glioma cell migration in a tenascin-C microenvironment. Cancer Research, 68, 6942–6952.PubMedGoogle Scholar
  91. 91.
    Orend, G., Huang, W., Olayioye, M. A., Hynes, N. E., & Chiquet-Ehrismann, R. (2003). Tenascin-C blocks cell-cycle progression of anchorage-dependent fibroblasts on fibronectin through inhibition of syndecan-4. Oncogene, 22, 3917–3926.PubMedGoogle Scholar
  92. 92.
    Ruiz, C., Huang, W., Hegi, M. E., Lange, K., Hamou, M. F., Fluri, E., et al. (2004). Growth promoting signaling by tenascin-C [corrected]. Cancer Research, 64, 7377–7385.PubMedGoogle Scholar
  93. 93.
    Crossin, K. L. (1996). Tenascin: A multifunctional extracellular matrix protein with a restricted distribution in development and disease. Journal of Cellular Biochemistry, 61, 592–598.PubMedGoogle Scholar
  94. 94.
    Prieto, A. L., Andersson-Fisone, C., & Crossin, K. L. (1992). Characterization of multiple adhesive and counteradhesive domains in the extracellular matrix protein cytotactin. Journal of Cell Biology, 119, 663–678.PubMedGoogle Scholar
  95. 95.
    Sriramarao, P., Mendler, M., & Bourdon, M. A. (1993). Endothelial cell attachment and spreading on human tenascin is mediated by alpha 2 beta 1 and alpha v beta 3 integrins. Journal of Cell Science, 105(Pt 4), 1001–1012.PubMedGoogle Scholar
  96. 96.
    Fischer, D., Tucker, R. P., Chiquet-Ehrismann, R., & Adams, J. C. (1997). Cell-adhesive responses to tenascin-C splice variants involve formation of fascin microspikes. Molecular Biology of the Cell, 8, 2055–2075.PubMedGoogle Scholar
  97. 97.
    Gotz, M., Bolz, J., Joester, A., & Faissner, A. (1997). Tenascin-C synthesis and influence on axonal growth during rat cortical development. European Journal of Neuroscience, 9, 496–506.PubMedGoogle Scholar
  98. 98.
    Hauzenberger, D., Olivier, P., Gundersen, D., & Ruegg, C. (1999). Tenascin-C inhibits beta1 integrin-dependent T lymphocyte adhesion to fibronectin through the binding of its fnIII 1–5 repeats to fibronectin. European Journal of Immunology, 29, 1435–1447.PubMedGoogle Scholar
  99. 99.
    Julian, J., Chiquet-Ehrismann, R., Erickson, H. P., & Carson, D. D. (1994). Tenascin is induced at implantation sites in the mouse uterus and interferes with epithelial cell adhesion. Development, 120, 661–671.PubMedGoogle Scholar
  100. 100.
    Krushel, L. A., Prieto, A. L., Edelman, G. M., & Crossin, K. L. (1994). Differential effects of cytotactin tenascin fusion proteins on intracellular pH and cell morphology. Journal of Cellular Physiology, 161, 508–518.PubMedGoogle Scholar
  101. 101.
    Spring, J., Beck, K., & Chiquet-Ehrismann, R. (1989). Two contrary functions of tenascin: Dissection of the active sites by recombinant tenascin fragments. Cell, 59, 325–334.PubMedGoogle Scholar
  102. 102.
    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. International Journal of Cancer, 52, 688–692.Google Scholar
  103. 103.
    Richter, P. T. M., Franz, M., Altendorf-Hofmann, A., Junker, K., Borsi, L., Neri, D., et al. (2009). B and C domain containing tenascin-C: Urinary markers for invasiveness of urothelial carcinoma of the urinary bladder? Journal of Cancer Research and Clinical Oncology, 135, 1351–1358.PubMedGoogle Scholar
  104. 104.
    Berndt, A., Anger, K., Richter, P., Borsi, L., Brack, S., Silacci, M., et al. (2006). Differential expression of tenascin-C splicing domains in urothelial carcinomas of the urinary bladder. Journal of Cancer Research and Clinical Oncology, 132, 537–546.PubMedGoogle Scholar
  105. 105.
    Herold-Mende, C., Mueller, M. M., Bonsanto, M. M., Schmitt, H. P., Kunze, S., & Steiner, H. H. (2002). Clinical impact and functional aspects of tenascin-C expression during glioma progression. International Journal of Cancer, 98, 362–369.Google Scholar
  106. 106.
    Gazzaniga, P., Nofroni, I., Gandini, O., Silvestri, I., Frati, L., Agliano, A. M., et al. (2005). Tenascin C and epidermal growth factor receptor as markers of circulating tumoral cells in bladder and colon cancer. Oncology Reports, 14, 1199–1202.PubMedGoogle Scholar
  107. 107.
    Parekh, K., Ramachandran, S., Cooper, J., Bigner, D., Patterson, A., & Mohanakumar, T. (2005). Tenascin-C, over expressed in lung cancer down regulates effector functions of tumor infiltrating lymphocytes. Lung Cancer, 47, 17–29.PubMedGoogle Scholar
  108. 108.
    Sis, B., Tuna, B., Yorukoglu, K., & Kargi, A. (2004). Tenascin C and cathepsin d expression in adipocytic tumors: an immunohistochemical investigation of 43 cases. International Journal of Surgical Pathology, 12, 11–15.PubMedGoogle Scholar
  109. 109.
    Vacca, A., Ribatti, D., Fanelli, M., Costantino, F., Nico, B., Di Stefano, R., et al. (1996). Expression of tenascin is related to histologic malignancy and angiogenesis in b-cell non-Hodgkin’s lymphomas. Leukemia and Lymphoma, 22, 473–481.PubMedGoogle Scholar
  110. 110.
    Pilch, H., Schaffer, U., Schlenger, K., Lautz, A., Tanner, B., Hockel, M., et al. (1999). Expression of tenascin in human cervical cancer-association of tenascin expression with clinicopathological parameters. Gynecologic Oncology, 73, 415–421.PubMedGoogle Scholar
  111. 111.
    Iskaros, B. E., Sison, C. P., & Hajdu, S. I. (2000). Tenascin patterns of expression in duct carcinoma in situ of the breast. Annals of Clinical and Laboratory Science, 30, 266–271.PubMedGoogle Scholar
  112. 112.
    Wilson, K. E., Langdon, S. P., Lessells, A. M., & Miller, W. R. (1996). Expression of the extracellular matrix protein tenascin in malignant and benign ovarian tumours. British Journal of Cancer, 74, 999–1004.PubMedGoogle Scholar
  113. 113.
    Meiners, S., Nur-e-Kamal, M. S., & Mercado, M. L. (2001). Identification of a neurite outgrowth-promoting motif within the alternatively spliced region of human tenascin-C. Journal of Neuroscience, 21, 7215–7225.PubMedGoogle Scholar
  114. 114.
    Mercado, M. L., Nur-e-Kamal, A., Liu, H. Y., Gross, S. R., Movahed, R., & Meiners, S. (2004). Neurite outgrowth by the alternatively spliced region of human tenascin-C is mediated by neuronal alpha7beta1 integrin. Journal of Neuroscience, 24, 238–247.PubMedGoogle Scholar
  115. 115.
    Rigato, F., Garwood, J., Calco, V., Heck, N., Faivre-Sarrailh, C., & Faissner, A. (2002). Tenascin-C promotes neurite outgrowth of embryonic hippocampal neurons through the alternatively spliced fibronectin type III BD domains via activation of the cell adhesion molecule F3/contactin. Journal of Neuroscience, 22, 6596–6609.PubMedGoogle Scholar
  116. 116.
    Cai, M., Onoda, K., Takao, M., Kyoko, I. Y., Shimpo, H., Yoshida, T., et al. (2002). Degradation of tenascin-C and activity of matrix metalloproteinase-2 are associated with tumor recurrence in early stage non-small cell lung cancer. Clinical Cancer Research, 8, 1152–1156.PubMedGoogle Scholar
  117. 117.
    Saito, Y., Imazeki, H., Miura, S., Yoshimura, T., Okutsu, H., Harada, Y., et al. (2007). A peptide derived from tenascin-C induces beta1 integrin activation through syndecan-4. Journal of Biological Chemistry, 282, 34929–34937.PubMedGoogle Scholar
  118. 118.
    Siri, A., Knauper, V., Veirana, N., Caocci, F., Murphy, G., & Zardi, L. (1995). Different susceptibility of small and large human tenascin-C isoforms to degradation by matrix metalloproteinases. Journal of Biological Chemistry, 270, 8650–8654.PubMedGoogle Scholar
  119. 119.
    Martin, D., Brown-Luedi, M., & Chiquet-Ehrismann, R. (2003). Tenascin-C signaling through induction of 14-3-3 tau. Journal of Cell Biology, 160, 171–175.PubMedGoogle Scholar
  120. 120.
    Sriramarao, P., & Bourdon, M. A. (1993). A novel tenascin type III repeat is part of a complex of tenascin mRNA alternative splices. Nucleic Acids Research, 21, 163–168.PubMedGoogle Scholar
  121. 121.
    Derr, L. B., Chiquet-Ehrismann, R., Gandour-Edwards, R., Spence, J., & Tucker, R. P. (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.PubMedGoogle Scholar
  122. 122.
    Tucker, R. P. (1998). Quantitative in situ localization of tenascin-C alternatively spliced transcripts in the avian optic tectum. Molecular Vision, 4, 18.PubMedGoogle Scholar
  123. 123.
    Guttery, D. S., Hancox, R. A., Mulligan, K. T., Hughes, S., Lambe, S. M., Pringle, J. H., et al. (2010). Association of invasion-promoting tenascin-C additional domains with breast cancer in young women. Breast Cancer Research, 12(4), R57.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of Cancer Studies and Molecular MedicineUniversity of LeicesterLeicesterUK

Personalised recommendations