@article {401,
	title = {Three-dimensional context regulation of metastasis.},
	journal = {Clin Exp Metastasis},
	volume = {26},
	year = {2009},
	month = {2009},
	pages = {35-49},
	abstract = {<p>Tumor progression ensues within a three-dimensional microenvironment that consists of cellular and non-cellular components. The extracellular matrix (ECM) and hypoxia are two non-cellular components that potently influence metastasis. ECM remodeling and collagen cross-linking stiffen the tissue stroma to promote transformation, tumor growth, motility and invasion, enhance cancer cell survival, enable metastatic dissemination, and facilitate the establishment of tumor cells at distant sites. Matrix degradation can additionally promote malignant progression and metastasis. Tumor hypoxia is functionally linked to altered stromal-epithelial interactions. Hypoxia additionally induces the expression of pro-migratory, survival and invasion genes, and up-regulates expression of ECM components and modifying enzymes, to enhance tumor progression and metastasis. Synergistic interactions between matrix remodeling and tumor hypoxia influence common mechanisms that maximize tumor progression and cooperate to drive metastasis. Thus, clarifying the molecular pathways by which ECM remodeling and tumor hypoxia intersect to promote tumor progression should identify novel therapeutic targets.</p>
},
	keywords = {Cell Division, Collagen, Disease Progression, Homeostasis, Humans, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplasms},
	issn = {1573-7276},
	doi = {10.1007/s10585-008-9209-8},
	author = {Erler, Janine T 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}
}
