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. 2005 Feb 24;24(9):1525-32. doi: 10.1038/sj.onc.1208342.


Tenascins represent a family of extracellular matrix glycoproteins with distinctive expression patterns. Here we have analyzed the most recently described member, tenascin-W, in breast cancer. Mammary tumors isolated from transgenic mice expressing hormone-induced oncogenes reveal tenascin-W in the stroma around lesions with a high likelihood of metastasis. The presence of tenascin-W was correlated with the expression of its putative receptor, alpha8 integrin. HC11 cells derived from normal mammary epithelium do not express alpha8 integrin and fail to cross tenascin-W-coated filters. However, 4T1 mammary carcinoma cells do express alpha8 integrin and their migration is stimulated by tenascin-W. The expression of tenascin-W is induced by BMP-2 but not by TGF-beta1, though the latter is a potent inducer of tenascin-C. The expression of tenascin-W is dependent on p38MAPK and JNK signaling pathways. Since preinflammatory cytokines also act through p38MAPK and JNK signaling pathways, the possible role of TNF-alpha in tenascin-W expression was also examined. TNF-alpha induced the expression of both tenascin-W and tenascin-C, and this induction was p38MAPK- and cyclooxygenase-dependent. Our results show that tenascin-W may be a useful diagnostic marker for breast malignancies, and that the induction of tenascin-W in the tumor stroma may contribute to the invasive behavior of tumor cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins / genetics*
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Integrin alpha Chains / physiology*
  • Oligonucleotide Array Sequence Analysis
  • Pituitary Neoplasms / genetics*
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / isolation & purification
  • Tenascin / analysis*
  • Tenascin / physiology*
  • Transforming Growth Factor beta / genetics*
  • Tumor Necrosis Factor-alpha / genetics*
  • p38 Mitogen-Activated Protein Kinases / metabolism*


  • BMP2 protein, human
  • Bmp2 protein, mouse
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Integrin alpha Chains
  • RNA, Neoplasm
  • Tenascin
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • integrin alpha8
  • p38 Mitogen-Activated Protein Kinases