Matrix metalloproteinases in tumor–host cell communication

• Published in: Differentiation (London) Vol. 70; no. 9; pp. 561 - 573
• Main Authors: Lynch, Conor C., Matrisian, Lynn M.
• Format: Journal Article
• Language: English
• Published: Berlin/Wien Elsevier B.V 01.12.2002; Blackwell Wissenschafts‐Verlag; Blackwell
• Subjects: Animals; Apoptosis - physiology; Biological and medical sciences; Cell differentiation, maturation, development, hematopoiesis; Cell Movement - physiology; Cell physiology; extracellular matrix (ECM); Fundamental and applied biological sciences. Psychology; host–tumor communication; Humans; matrix metalloproteinases (MMPs); Matrix Metalloproteinases - metabolism; Mice; Mitogens - metabolism; Molecular and cellular biology; Neoplasms - metabolism; Neoplastic Processes; Neovascularization, Pathologic - metabolism; Signal Transduction - physiology; Substrate Specificity; matrix metalloproteinases (MMPs); extracellular matrix (ECM); host–tumor communication; Human; host-tumor communication; Enzyme; Interaction; Stroma; Review; Microenvironment; Malignant tumor; Gene expression; Carcinogenesis; Peptidases; Hydrolases; Extracellular matrix; Tumor
• ISSN: 0301-4681; 1432-0436
• DOI: 10.1046/j.1432-0436.2002.700909.x

The microenvironment or stroma immediately surrounding tumor cells consists of a three-dimensional extracellular matrix (ECM) and stromal cells such as fibroblasts and inflammatory cells. The matrix metalloproteinases (MMPs) constitute a family of over 24 members, which collectively are capable of degrading virtually the entire ECM. Strict regulation of MMP expression is critical in order to maintain proper ECM homeostasis, but in disease states such as cancer there is often a high level of MMP activity at the tumor–stroma interface. Several studies have documented the importance of MMP-mediated ECM destruction in the successful dissemination of several tumor types, but it has become increasingly clear that they are also involved in earlier stages of tumorigenesis. MMPs are implicated in a wide variety of roles that can assist tumor initiation, growth, migration, angiogenesis, the selection of apoptosis-resistant subpopulations, and in invasion and metastasis. Interestingly, the factors responsible for many of these effects are derived from the cell surfaces of the tumor or stromal cells or are embedded in the ECM. Therefore, the MMPs can no longer be thought of solely as ECM destructionists, but as part of an elegant communication system through which the tumor interacts with the stroma.