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 language | English (US) |
|---|---|
| Pages (from-to) | 1525-1532 |
| Number of pages | 8 |
| Journal | Oncogene |
| Volume | 24 |
| Issue number | 9 |
| DOIs | |
| State | Published - 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
Cite this
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. / Scherberich, Arnaud; Tucker, Richard P; Degen, Martin; Brown-Luedi, Marianne; Andres, Anne Catherine; Chiquet-Ehrismann, Ruth.
In: Oncogene, Vol. 24, No. 9, 24.02.2005, p. 1525-1532.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - 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
AU - Scherberich, Arnaud
AU - Tucker, Richard P
AU - Degen, Martin
AU - Brown-Luedi, Marianne
AU - Andres, Anne Catherine
AU - Chiquet-Ehrismann, Ruth
PY - 2005/2/24
Y1 - 2005/2/24
N2 - 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.
AB - 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.
KW - α8 integrin
KW - Breast cancer
KW - Extracellular matrix
KW - p38
KW - Tumor stroma
UR - http://www.scopus.com/inward/record.url?scp=14944345010&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=14944345010&partnerID=8YFLogxK
U2 - 10.1038/sj.onc.1208342
DO - 10.1038/sj.onc.1208342
M3 - Article
C2 - 15592496
AN - SCOPUS:14944345010
VL - 24
SP - 1525
EP - 1532
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 9
ER -