Contributions of tumor and stromal matrix metalloproteinases to tumor progression, invasion and metastasis.
The malignant progression of tumors is driven by the expression of oncogenes and loss of expression of tumor suppressor genes; factors that are intrinsic to cancer cells. The phenotypic changes brought about by the gain or loss of expression of oncogenes and tumor suppressor genes lead to the acquisition of malignant traits, namely, the ability to invade into and grow in ectopic tissue environments. Recently, however, focus in cancer research has widened from the cancer cell to include the surrounding tumor stroma as an integral player in the process of tumor progression. One of the areas in cancer research contributing to this enhanced appreciation of stromal involvement in tumor progression and metastasis is that of matrix metalloproteinases (MMPs). This review provides an overview of the characteristics of MMPs and discusses their role in the progression and metastasis of tumors. Initially, attention will focus on the regulation of MMPs in tumor cells but will switch to discourse on stromal expression of MMPs in tumors and speculation on the functional consequences of stromal expression of MMPs.
MacDougall
J R
JR
Department of Cell Biology, Vanderbilt University, Nashville, Tennessee 37232-2175, USA.
Matrisian
L M
LM
D000595:Amino Acid Sequence; D018450:Disease Progression; D005109:Extracellular Matrix / Q000201:enzymology*; D008666:Metalloendopeptidases / Q000502:physiology*; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology; D017154:Stromal Cells / Q000201:enzymology
D008666:Metalloendopeptidases