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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

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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.

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Acknowledgements

This research was supported by grants from the Novartis Research Foundation and the Krebsliga beider Basel (A Scherberich) and the National Science Foundation (0235711; RP Tucker).

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Authors and Affiliations

  1. Novartis Research Foundation, Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, CH-4058, Basel, Switzerland

    Arnaud Scherberich, Martin Degen, Marianne Brown-Luedi & Ruth Chiquet-Ehrismann

  2. Department of Cell Biology and Human Anatomy, University of California at Davis, Davis, CA, 95616, USA

    Richard P Tucker

  3. Department of Clinical Research, Faculty of Medicine, University of Bern, Tiefenaustrasse 120, CH-3004, Bern, Switzerland

    Anne-Catherine Andres

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  1. Arnaud Scherberich
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  2. Richard P Tucker
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Correspondence to Ruth Chiquet-Ehrismann.

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Scherberich, A., Tucker, R., Degen, M. et al. 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 (2005). https://doi.org/10.1038/sj.onc.1208342

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