In Vivo Analysis of Alternative Modes of Breast Cancer Cell Invasion
Abstract
The purpose of this funded research program is to examine different modes of movement used by mammary tumor cells during local invasion and metastasis. In year 2 of the program I have expanded upon the role of Rho/ROCK signaling in driving tumor cell migration and invasion. Specifically, I have found that collagen I, a component of aggressive primary human breast tumors, promotes an invasive phenotype in a 3D culture system. Collagen I promotes invasion through an increase in actomyosin contractility in MMTV-neu-derived mouse mammary tumor cells. Interestingly, a highly contractile phenotype is normally restricted to myoepithelial/basal cells of the mammary gland, as well as the more aggressive basal-like breast cancers. I have experimental evidence, therefore, that collagen I may be promoting a more aggressive basal clinical subtype in primary breast tumors. In addition, I have found that MMTV-neu-derived cells express markers of the epithelial mesenchymal transition (EMT), yet are non-invasive in Matrigel reconstituted basement membrane. In the presence of collagen I, however, the cells acquire a highly motile mesenchymal phenotype. These results suggest that the invasive properties of mammary tumors depends on the extracellular matrix environment, through an impact on Rho/ROCK signaling.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2009
- Accession Number
- ADA542372
Entities
People
- Donald E. White
Organizations
- University of London