@article {376,
	title = {Multiscale modeling of form and function.},
	journal = {Science},
	volume = {324},
	year = {2009},
	month = {2009 Apr 10},
	pages = {208-12},
	abstract = {<p>Topobiology posits that morphogenesis is driven by differential adhesive interactions among heterogeneous cell populations. This paradigm has been revised to include force-dependent molecular switches, cell and tissue tension, and reciprocal interactions with the microenvironment. It is now appreciated that tissue development is executed through conserved decision-making modules that operate on multiple length scales from the molecular and subcellular level through to the cell and tissue level and that these regulatory mechanisms specify cell and tissue fate by modifying the context of cellular signaling and gene expression. Here, we discuss the origin of these decision-making modules and illustrate how emergent properties of adhesion-directed multicellular structures sculpt the tissue, promote its functionality, and maintain its homeostasis through spatial segregation and organization of anchored proteins and secreted factors and through emergent properties of tissues, including tension fields and energy optimization.</p>
},
	keywords = {Animals, Biological Evolution, Cell Adhesion, Cell Aggregation, Cell Communication, Extracellular Matrix, Genotype, Homeostasis, Morphogenesis, Phenotype, Proteins, Signal Transduction},
	issn = {1095-9203},
	doi = {10.1126/science.1170107},
	author = {Engler, Adam J and Humbert, Patrick O and Wehrle-Haller, Bernhard and Weaver, Valerie M}
}
@article {561,
	title = {Reversion of the malignant phenotype of human breast cells in three-dimensional culture and in vivo by integrin blocking antibodies.},
	journal = {J Cell Biol},
	volume = {137},
	year = {1997},
	month = {1997 Apr 7},
	pages = {231-45},
	abstract = {<p>In a recently developed human breast cancer model, treatment of tumor cells in a 3-dimensional culture with inhibitory beta1-integrin antibody or its Fab fragments led to a striking morphological and functional reversion to a normal phenotype. A stimulatory beta1-integrin antibody proved to be ineffective. The newly formed reverted acini re-assembled a basement membrane and re-established E-cadherin-catenin complexes, and re-organized their cytoskeletons. At the same time they downregulated cyclin D1, upregulated p21(cip,wat-1), and stopped growing. Tumor cells treated with the same antibody and injected into nude mice had significantly reduced number and size of tumors in nude mice. The tissue distribution of other integrins was also normalized, suggesting the existence of intimate interactions between the different integrin pathways as well as adherens junctions. On the other hand, nonmalignant cells when treated with either alpha6 or beta4 function altering antibodies continued to grow, and had disorganized colony morphologies resembling the untreated tumor colonies. This shows a significant role of the alpha6/beta4 heterodimer in directing polarity and tissue structure. The observed phenotypes were reversible when the cells were disassociated and the antibodies removed. Our results illustrate that the extracellular matrix and its receptors dictate the phenotype of mammary epithelial cells, and thus in this model system the tissue phenotype is dominant over the cellular genotype.</p>
},
	keywords = {Animals, Antibodies, Monoclonal, Antigens, CD, Antigens, CD29, Basement Membrane, Binding, Competitive, Breast Neoplasms, Cell Division, Extracellular Matrix, Female, Fluorescent Antibody Technique, Genotype, Humans, Immunoglobulin Fab Fragments, Integrin beta4, Mice, Phenotype, Rats, Signal Transduction, Transformation, Genetic, Tumor Cells, Cultured},
	issn = {0021-9525},
	author = {Weaver, V M and Petersen, O W and Wang, F and Larabell, C A and Briand, P and Damsky, C and Bissell, M J}
}
