@article {326,
	title = {Engineering strategies to recapitulate epithelial morphogenesis within synthetic three-dimensional extracellular matrix with tunable mechanical properties.},
	journal = {Phys Biol},
	volume = {8},
	year = {2011},
	month = {2011 Apr},
	pages = {026013},
	abstract = {<p>The mechanical properties (e.g. stiffness) of the extracellular matrix (ECM) influence cell fate and tissue morphogenesis and contribute to disease progression. Nevertheless, our understanding of the mechanisms by which ECM rigidity modulates cell behavior and fate remains rudimentary. To address this issue, a number of two and three-dimensional (3D) hydrogel systems have been used to explore the effects of the mechanical properties of the ECM on cell behavior. Unfortunately, many of these systems have limited application because fiber architecture, adhesiveness and/or pore size often change in parallel when gel elasticity is varied. Here we describe the use of ECM-adsorbed, synthetic, self-assembling peptide (SAP) gels that are able to recapitulate normal epithelial acini morphogenesis and gene expression in a 3D context. By exploiting the range of viscoelasticity attainable with these SAP gels, and their ability to recreate native-like ECM fibril topology with minimal variability in ligand density and pore size, we were able to reconstitute normal and tumor-like phenotypes and gene expression patterns in nonmalignant mammary epithelial cells. Accordingly, this SAP hydrogel system presents the first tunable system capable of independently assessing the interplay between ECM stiffness and multi-cellular epithelial phenotype in a 3D context.</p>
},
	keywords = {Biomechanical Phenomena, Epithelium, Extracellular Matrix, Gene Expression, Humans, Hydrogels, Morphogenesis, Peptides, Porosity, Tissue Engineering},
	issn = {1478-3975},
	doi = {10.1088/1478-3975/8/2/026013},
	author = {Miroshnikova, Y A and Jorgens, D M and Spirio, L and Auer, M and Sarang-Sieminski, A L and Weaver, V M}
}
@article {566,
	title = {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.},
	journal = {Biochem Cell Biol},
	volume = {74},
	year = {1996},
	month = {1996},
	pages = {833-51},
	abstract = {<p>The extracellular matrix (ECM) is a dominant regulator of tissue development and homeostasis. \&quot;Designer microenvironments\&quot; 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.</p>
},
	keywords = {Animals, Breast Neoplasms, Cell Adhesion, Epithelium, Extracellular Matrix, Humans, Models, Biological, Tumor Cells, Cultured},
	issn = {0829-8211},
	author = {Weaver, V M and Fischer, A H and Peterson, O W and Bissell, M J}
}
