The main goal of this study is to identify probes/markers for epithelial to mesenchymal transformed (EMT) breast cancer cells. Epithelial to Mesenchymal transition of cancer cells is a crucial phenomenon demonstrated by the epithelial type cancer cells in order to invade, and metastasize to distant organs. It is a process of loss of epithelial characteristics and the acquisition of a mesenchymal-like phenotype of cancer cells. It is thought to precede and enable the dissemination of tumor cells into the surrounding tissue and circulation. However characterization of these transformed cells has been challenging because of the non-specificity of the mesenchymal markers used to define them. So the picture of EMT and subsequent invasion is relatively unclear and warrants a more ambitious set of specific markers that can identify these transformed cell population and distinguish them from other mesenchymal cells such as fibroblasts. A new challenge, within this frame of concept, is to find specific set of biomarkers relevant for this process. We propose a novel and innovative study to use phage display libraries for identification of phages that can specifically and selectively bind to the EMT transitioned breast cancer cells invitro, in human breasts cancer tissues and help to distinguish them from the surrounding fibroblasts. This whole study is directed to obtain phage ligands binding to EMT-specific breast cancer cells. The project will include: 1) Selection and characterization phages that bind with high affinity, selectivity and specificity to the panel of human metastatic breast cancer cells after subtractive screening against mammary carcinoma- associated fibroblasts (CAF's). 2) Testing the binding of the selected phages to EMT-induced models of breast cancer cells and 3) Testing the binding of the selected phages to human breast cancer tissue (exvivio). Successful accomplishment of this project would lead to the development of the novel generation of phage-derived probes that can be further used for diagnostics, therapy, profiling and imaging.
The goal of this proposal is to contribute to the study and complex mechanism of breast tumor invasion, dissemination and metastasis via identifying one of the early events, epithelial to mesenchymal transition of cancer cells, by selecting phages probes that can recognize these transitioned cells with high specificity and selectivity. The important outcome of this study may be the development of EMT-specific biomarkers that can be used clinically to define the onset of metastasis and circulating tumor cells.
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| Henderson, Henry J; Karanam, Balasubramanyam; Samant, Rajeev et al. (2017) Neuroligin 4X overexpression in human breast cancer is associated with poor relapse-free survival. PLoS One 12:e0189662 |
