Year: 2006
Type: article
Abstract: Cellular interactions with the extracellular matrix (ECM) control many aspects of cell function. The complex ECM protein Tenascin-C (TN), which exists as multiple isoforms, is upregulated in breast cancer. We previously have identified a change in the TN isoform profile in breast cancer, with detection of two additional isoforms — TN16 and TN14/16 — not seen in normal breast [ 1 ]. The purpose of this study was to investigate directly the effects of these tumour-associated TNC isoforms on breast cancer cell behaviour. A PCR-ligation approach was used to generate specific TNC isoform sequences which were Flag tagged and inserted into a pCMV vector. Transient transfection into breast cancer cell lines or primary normal fibroblasts was confirmed by RT-PCR, western blotting and immunohistochemistry. The effect of different TNC isoforms on breast cancer cell invasion, proliferation and gene expression was analysed. Expression of TN16 and TN14/16 in breast cancer cells (MCF-7, T47D, MDAMB231) resulted in significantly enhanced tumour invasion compared with adult-type truncated TN, large TN and vector-only controls. A similar increase in tumour cell proliferation was detected. Coculture of tumour cells with primary breast fibroblasts overexpressing TN16 or TN14/16 or conditioned medium from these fibroblasts also led to enhanced tumour cell invasion. Expression of TN resulted in upregulation of MMP-1; however, this was equivalent for all TN isoforms. The invasion-promoting effect of TN16 and TN14/16 was dependent on direct interaction between tumour cells and was blocked by incorporation of anti-TN blocking antibodies. Furthermore, TN appears to be essential for tumour cell invasion, since with all isoforms invasion was minimal in the presence of anti-TN antibodies. This study has demonstrated that the tumour-associated TN isoforms TN16 and TN14/16 significantly enhance breast cancer cell invasion and that blocking TN inhibits invasion. We aim to further investigate the invasion-promoting activity of these isoforms and to explore their therapeutic potential in more sophisticated tumour models.
Source: Breast Cancer Research
DOI: 10.1186/bcr1575
Institutions: University of Leicester, Queen Mary University of London
Language: Italian
Subfield: Immunology and Allergy
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,190
Funders: Royal College of Pathologists of Australasia, University of Dundee, University of Essex, Wellcome Trust, Cancer and Polio Research Fund, Cancer Research UK, Breast Cancer Campaign, Breast Cancer Research Trust, King's College London, University of Sheffield, University of Kent, Cambridge University Hospitals, Medical Research Council, World Cancer Research Fund, Japan Society for the Promotion of Science, National Cancer Institute
OpenAlex ID: W1720320355