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MT1-MMP in Cancer Metastasis: Novel Bi-Functional Peptide in Cancer Imaging

Tumor metastasis is responsible for 90% of all cancer deaths, yet remains one of the most poorly understood aspects of the pathophysiology of cancer progression. Although it remains to be fully understood, emerging evidence has indicated that metastatic cancer stem cells (CSCs)/tumor initiating cells (TICs) posses both a stem cell phenotype and an invasive ability. Most human cancers are epithelial in origin and transition of human cancers to a metastatic phenotype often involves the loss of their epithelial phenotype and the gain of a fibroblastic or mesenchymal phenotype (epithelial-to-mesenchymal transition, EMT). The EMT has been linked to a pathway that confers both metastatic and self-renewal properties on breast tumor cells. Experimental evidence also suggests that the EMT is transient and can be reversed upon removing stimulating factors. Consistent with this concept, pathologic examination of human cancer tissues reveals remarkable resemblances between primary and metastatic tumors. However, the specific molecular mechanisms for these transitions are poorly understood.

In collaboration with Prof. Jian Cao, our long-term goal is to inhibit cancer cell migration and invasion, and hence to prevent cancer metastasis. Our overall objective is to understand the interplay between cancer cells and their microenvironment in the transition to invasion and metastasis; and to develop diagnostic tools to identify early human cancers. We are studying MT1-MMP, a key molecule capable of reprogramming epithelial cancer stem cells and mesenchymal-like cells at different stages of tumor dissemination. Its expression profile suggests that MT1-MMP may be a useful biomarker in cancer diagnosis. Development of an imaging probe recognizing MT1-MMP will permit early stage cancer diagnosis. We are currently developing a peptide that inhibits MT1-MMP cell surface interactions into non-invasive imaging agents of MT1-MMP expression in living subjects. Current projects are focused on PET imaging methods and exploring the use of the inhibitor peptide as a tumor-targeting agent.



 
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