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

Arnaud Scherberich, Richard P Tucker, Martin Degen, Marianne Brown-Luedi, Anne Catherine Andres, Ruth Chiquet-Ehrismann

Research output: Contribution to journalArticle

58 Scopus citations

Abstract

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, α8 integrin. HC11 cells derived from normal mammary epithelium do not express α8 integrin and fail to cross tenascin-W-coated filters. However, 4T1 mammary carcinoma cells do express α8 integrin and their migration is stimulated by tenascin-W. The expression of tenascin-W is induced by BMP-2 but not by TGF-β1, 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-α in tenascin-W expression was also examined. TNF-α 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.

Original languageEnglish (US)
Pages (from-to)1525-1532
Number of pages8
JournalOncogene
Volume24
Issue number9
DOIs
StatePublished - Feb 24 2005

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Keywords

  • α8 integrin
  • Breast cancer
  • Extracellular matrix
  • p38
  • Tumor stroma

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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