Revealing the Functions of Tenascin-C in 3-D Breast Cancer Models Using Cell Biological and In Silico Approaches
Abstract
The extracellular matrix (ECM) glycoprotein tenascin-C (TN-C) has already been implicated in both breast cancer development and progression (Jones, 2001 & Jakhola,1998). TN-C has also been independently linked to poor prognosis in breast cancer (Suwiwat, 2004). However, the mechanisms by which TN-C exerts its effects on human mammary epithelial cells within an appropriate tissue context have not been elucidated. The purpose of this training grant is to determine the mechanism by which TN-C perturbs normal tissue architecture in three-dimensional (3-D) organotypic cultures of human mammary epithelial cells by focusing on cell-cell junctions, adherens junctions in particular, as well as activation of receptor tyrosine kinases, namely EGFR and c-met. Furthermore, as 3-D organotypic cultures are becoming more widely used in the biological community, we sought to develop a computational tool for objective evaluation of three-dimensional (3-D) architecture in organotypic cultures, in order to be able to determine the global effects of TN-C and other ECM components as well as oncogenes on overall tissue architecture. By elucidating the effects of TN-C on tissue architecture and gaining insights into the mechanisms involved, we hope to better understand how to rationally target the ECM, and TN-C in particular, for therapy in premalignant and malignant breast lesions.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2007
- Accession Number
- ADA469364
Entities
People
- Agne Taraseviciute
- Peter L. Jones
Organizations
- University of Pennsylvania