ABSTRACT: Expression of tissue factor (TF), the cellular receptor of clotting factor VII/VIIa, is a feature of certain malignant tumours.
The TF gene has been classified as an immediate early gene responsive to serum and cytokines. Thus, the regulation of TF gene
expression seems to play a role in cell growth. Recently, we have shown that constitutive TF expression in MCF-7 breast cancer
cells is modulated by such growth factors as EGF, TGFα, and IL-1. The present study deals with the immunocytochemically detectable
cellular distribution of TF in human breast cancer cell lines MCF-7 and MaTu stimulated by EGF and TGFα. In MCF-7 cells growing
logarithmically, stimulation led to a significant increase of TF mRNA after 2 h (in situ hybridization, Northern blot) and
to maximum TF expression after 6 h (immunohistochemistry). When decorated by monoclonal antibodies, TF protein showed a pronounced
localization at ruffled membrane areas, cell edges, and processes of spreading cells after 6 and 20 h. In more flattened cells
TF was concentrated in peripheric lamellae and microspikes communicating with neighbouring cells. After epithelial colony
pattern had established, TF was predominantly accumulated at the intercellular boundaries. The vary same distribution patterns
as seen in MCF-7 cells were true for the stimulated MaTu cell line. The dynamics and cellular distribution patterns of stimulated
TF expression support the hypothesis that TF could be of importance for morphogenic events associated with the growth and
differentiation of breast cancer cells in culture.
Virchows Archiv B Cell Pathology 11/1993; 64(1):265-269.