Imaging the Vascular and Metabolic Impact of Claudin-7, a Tight Junction Protein in Transgenic Human Breast Cancer Models

摘要

Through the application of SAGE and array technologies, our laboratory has identified genes, such as Claudin-7, that are lost in metastatic breast cancer cells. We plan to apply magnetic resonance imaging and spectroscopy to determine the impact of Claudin-7 on breast cancer cell invasion and metabolism. Breast cancer cells engineered to stably overexpress Claudin-7 will be generated. MR microscopy methods will be used to quantify invasion of cells into Matrigel and localized 1H MRS and 31P MRS will be used to study the physiology and metabolism of cells during invasion Alterations in tight junction characteristics will be analyzed to study correlation to the acquired phenotypes. To characterize vasculature in terms of vascular volume and permeability using high resolution MRI, tumor metabolic characteristics, namely, lactate levels, intra- and extra-cellular pH, and phospholipid metabolism will be obtained by multi-nuclear (1H and 31P) spectroscopic imaging of solid tumors These aims will be performed using the following human breast cancer cell lines: non-metastatic cell lines MCF-7 and SKBR3, and the metastatic cell line, MDA-MB- 435.