The importance of the microenvironment in breast cancer progression: recapitulation of mammary tumorigenesis using a unique human mammary epithelial cell model and a three-dimensional culture assay.

TitleThe importance of the microenvironment in breast cancer progression: recapitulation of mammary tumorigenesis using a unique human mammary epithelial cell model and a three-dimensional culture assay.
Publication TypeJournal Article
Year of Publication1996
AuthorsWeaver VM, Fischer AH, Peterson OW, Bissell MJ
JournalBiochem Cell Biol
Volume74
Issue6
Pagination833-51
Date Published1996
ISSN0829-8211
KeywordsAnimals, Breast Neoplasms, Cell Adhesion, Epithelium, Extracellular Matrix, Humans, Models, Biological, Tumor Cells, Cultured
Abstract

The extracellular matrix (ECM) is a dominant regulator of tissue development and homeostasis. "Designer microenvironments" in culture and in vivo model systems have shown that the ECM regulates growth, differentiation, and apoptosis in murine and human mammary epithelial cells (MEC) through a hierarchy of transcriptional events involving the intricate interplay between soluble and physical signaling pathways. Furthermore, these studies have shown that these pathways direct and in turn are influenced by the tissue structure. Tissue structure is directed by the cooperative interactions of the cell-cell and cell-ECM pathways and can be modified by stromal factors. Not surprisingly then, loss of tissue structure and alterations in ECM components are associated with the appearance and dissemination of breast tumors, and malignancy is associated with perturbations in cell adhesion, changes in adhesion molecules, and a stromal reaction. Several lines of evidence now support the contention that the pathogenesis of breast cancer is determined (at least in part) by the dynamic interplay between the ductal epithelial cells, the microenvironment, and the tissue structure (acini). Thus, to understand the mechanisms involved in carcinogenesis, the role of the microenvironment (ECM as well as the stromal cells) with respect to tissue structure should be considered and studied. Towards this goal, we have established a unique human MEC model of tumorigenesis, which in concert with a three-dimensional assay, recapitulates many of the genetic and morphological changes observed in breast in cancer in vivo. We are currently using this system to understand the role of the microenvironment and tissue structure in breast cancer progression.

Alternate JournalBiochem. Cell Biol.
PubMed ID9164652
PubMed Central IDPMC2933195
Grant ListCA-64786 / CA / NCI NIH HHS / United States
R01 CA064786-05 / CA / NCI NIH HHS / United States