Breast Cancer in Context: New Tools and Paradigms for the Millennium
Abstract
We hypothesized that breast tumors are capable of multiple differentiation pathways. A finite number of interconnected pathways establish homeostasis in normal tissues which, if still functional in tumors, may be manipulated for therapy. Our goal was to characterize a large number of breast cancer cell lines with known genomic profiles as surrogates for human breast cancers utilizing a robust 3-dimensional assay with laminin-rich extracellular matrix (3D lrECM) with the aim of discovering new pathways to be targeted by combinations of drugs. In this assay non-malignant mammary epithelial cells form breast-like acinar structures whereby cells growth arrest and polarize while tumorigenic cells proliferate as a disorganized mass. Tumor cells treated with a number of signaling inhibitors alone or in combination are phenotypically reverted or killed. We have found that tumor cell lines adopt one of 4 distinct 3D morphologies which provide a finer delineation than hierarchical clustering of expression profiles of cell lines in 2D alone and that these morphologies may be reflective of their biological origin and phenotypic properties, such as degree of invasiveness. We have also found that the 3D microenvironment exerts common changes in expression profiles across all cell lines that are associated with signal transduction activity. Most importantly, we have shown that response to chemotherapeutic agents and radiation are fundamentally different in 2D and 3D assays with the latter more closely predicting in vivo response.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2007
- Accession Number
- ADA474575
Entities
People
- Mina Bissell
Organizations
- University of California, Berkeley