Tenascin-C modulates tumor stroma and monocyte/macrophage recruitment but not tumor growth or metastasis in a mouse strain with spontaneous mammary cancer.
The local growth of tumors and their ability to metastasize are crucially dependent on their interactions with the surrounding extracellular matrix. Tenascin-C (TNC) is an extracellular matrix protein which is highly expressed during development, tissue repair and cancer. Despite the high levels of TNC in the stroma of primary and metastatic tumors, the function of TNC is not known. In the present study we have crossed TNC-null mice with a mouse strain where both female and male mice spontaneously develop mammary tumors followed by metastatic disease in the lungs. We report that the absence of TNC had no effect on the temporal occurrence of mammary tumors and their metastatic dissemination in lungs. Furthermore, the number and size of tumors, the number and size of metastatic foci in the lungs, the proliferation rate and apoptosis of tumor cells and tumor angiogenesis were not altered in the absence of TNC. Histological examination revealed that the tumor organisation, however, was modulated by TNC. In the presence of TNC both primary as well as metastatic tumors were organised in large tumor cell nests surrounded by thick layers of extracellular matrix proteins. In the absence of TNC these tumor cell nests were smaller but still separated from each other by extracellular matrix proteins. In addition, the TNC-null stromal compartment contained significantly more monocytes/macrophages than tumor stroma from TNC wild-type mice. Using in vitro coculture experiments we show that TNC-null tumor cells were still able to activate the TNC gene in fibroblasts which express low basal levels of TNC. Altogether these data indicate that TNC has a very limited role during the spontaneous development and growth of mamary tumors and their metastasis to the lungs.
Talts
J F
JF
Max-Planck-Institute of Biochemistry, Department of Protein Chemistry, Germany.
Wirl
G
G
Dictor
M
M
Muller
W J
WJ
Fässler
R
R
D000818:Animals; D002455:Cell Division / Q000502:physiology; D018920:Coculture Techniques; D005260:Female; D008175:Lung Neoplasms / Q000503:physiopathology / Q000556:secondary; D008264:Macrophages / Q000473:pathology / Q000502:physiology*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D009000:Monocytes / Q000473:pathology / Q000502:physiology*; D017154:Stromal Cells / Q000473:pathology / Q000502:physiology; D019063:Tenascin / Q000502:physiology*
D019063:Tenascin