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Alexia ARPEL

Dernière mise à jour : jeudi 5 janvier 2012, par Patrick BARD


SPECT imaging of ErbB2 and Tenascin –C in a murine breast cancer model

Breast cancer is the most frequent cancer in women. At a progressed stage, the disease shows a high risk of metastasis to bone, liver and lung which results in a virtually incurable condition. The tumor microenvironment is instrumental in breast cancer metastasis and a high expression on the extracellular matrix (ECM) molecule tenascin-C (TNC) was shown to be causally linked to lung metastasis in an experimental murine xenographt tumor model. High TNC expression is linked to a bad prognosis of patients with brain, lung and breast cancer. Its high expression also correlated with a shortened metastasis-free survival and a reduced responsiveness towards tamoxifen in estrogen receptor positive breast cancer patients.
To interfere with lung metastasis novel means are needed to detect metastasis earlier. Drugs targeting TNC are currently developed and some drugs have already reached advanced clinical trials (1). We had developed a novel peptide that binds TNC and neutralizes the effect of TNC on cell adhesion. This peptide will be used for live imaging of breast cancer in a stochastic breast cancer model with ectopic TNC expression in compound ErbB2 overexpressing tumor mice (MMTV-NeuNT/TNC) that we had developed.
Overexpression of ErbB2 characterizes a subset of very aggressive breast cancers and patients with activated ErbB2 benefit from targeting ErbB2 with the antibody herceptin. But a prolonged treatment triggers resistance against herceptin, which creates the need to develop other tools that independently target these cancers. We had established a small peptide targeting the transmembrane domain of ErbB2 that specifically prevented dimerization of the ErB2 receptor and thus blocked corresponding downstream signalling. Here the TNC and the ErbB2 targeting peptides will be labelled with infrared fluorphore (NightOwl detection) together with 135I to perform non invasive Single Photon Emission Computed Tomography (SPECT) imaging. The multimodal platform that will be used for small animal imaging SPECT-CT (computed tomography) allows to generate simultaneously an anatomic 3D image (CT) that can be combined with a functional 3D image (SPECT). It will be determine whether the ErbB2 targeting peptide has an impact on ErbB2-driven tumorigenesis and metastasis in the MMTV-NeuNT model. This study will show whether the TNC- and ErbB2 peptide can be used for non-invasive live detection of breast cancer and metastasis and whether the peptides have an effect on breast cancer progression. The long-term goal is the transfer of this knowledge into the clinics for an earlier detection of breast cancer metastasis.