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Microenvironmental regulators of tissue structure and function also regulate tumor induction and progression: the role of extracellular matrix and its degrading enzymes.
| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Bissell, M. J. Kenny, P. A. Radisky, D. C. |
| Description | Country affiliation: United States Author Affiliation: Bissell MJ ( Cancer Biology Department, Life Sciences Division, Lawrence Berkeley National Laboratory, University of California, 94720, USA.) |
| Abstract | It is now widely accepted that elements of the cellular and tissue microenvironment are crucial regulators of cell behavior in culture and homeostasis in vivo, and that many of the same factors influence the course of tumor progression. Less well established is the extent to which extracellular factors actually cause cancer, and the circumstances under which this may occur. Using physiologically relevant three-dimensional culture assays and transgenic animals, we have explored how the environmental and architectural context of cells, tissues, and organs controls mammary-specific gene expression, growth regulation, apoptosis, and drug resistance and have found that loss of tissue structure is a prerequisite for cancer progression. Here we summarize this evidence and highlight two of our recent studies. Using mouse mammary epithelial cells, we show that exposure to matrix metalloproteinase-3 (MMP-3) stimulates production of reactive oxygen species (ROS) that destabilize the genome and induce epithelial-mesenchymal transition, causing malignant transformation. Using a human breast cancer progression series, we find that ADAM-dependent growth factor shedding plays a crucial role in acquisition of the malignant phenotype. These findings illustrate how normal tissue structure controls the response to extracellular signals so as to preserve tissue specificity and growth status. |
| File Format | HTM / HTML |
| ISSN | 00917451 |
| e-ISSN | 19434456 |
| Journal | Cold Spring Harbor Symposia on Quantitative Biology |
| Volume Number | 70 |
| Language | English |
| Publisher | Cold Spring Harbor Laboratory Press |
| Publisher Date | 2005-01-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Discipline Biology Extracellular Matrix Physiology Neoplasms Etiology Animals Breast Pathology Physiopathology Breast Neoplasms Cell Shape Cell Transformation, Neoplastic Enzymology Mammary Glands, Animal Mammary Neoplasms, Experimental Metalloproteases Genetics Mice Oncogenes Polymorphism, Genetic Signal Transduction Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Research Support, U.s. Gov't, Non-p.h.s. |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics Biochemistry Molecular Biology |
