Selective Modulation of Collagenase 1 Gene Expression by the Chemotherapeutic Agent Doxorubicin

Matrix metalloproteinases (MMPs) play a crucial role in tumor cell invasion and metastasis due to their ability to digest basement membrane and extracellular matrix components, thereby facilitating cell movement through connective tissues. At noncytotoxic concentrations, i.e. , concentrations lower...

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Bibliographic Details
Published in:Clinical cancer research 1999-01, Vol.5 (1), p.203-208
Main Authors: BENBOW, U, MAITRA, R, HAMILTON, J. W, BRINCKERHOFF, C. E
Format: Article
Language:English
Subjects:
Antineoplastic agents
Antineoplastic Agents - pharmacology
ATP-Binding Cassette, Sub-Family B, Member 1 - biosynthesis
Biological and medical sciences
Cell Division - drug effects
Chemotherapy
Collagen
Collagenases - biosynthesis
Collagenases - genetics
Doxorubicin - pharmacology
Gelatinases - biosynthesis
Gene Expression Regulation, Neoplastic - drug effects
Humans
Matrix Metalloproteinase 1
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Medical sciences
Melanoma
Metalloendopeptidases - biosynthesis
Neoplasm Invasiveness
Neoplasm Metastasis
Pharmacology. Drug treatments
RNA, Messenger - metabolism
Tumor Cells, Cultured
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Summary:Matrix metalloproteinases (MMPs) play a crucial role in tumor cell invasion and metastasis due to their ability to digest basement membrane and extracellular matrix components, thereby facilitating cell movement through connective tissues. At noncytotoxic concentrations, i.e. , concentrations lower than those normally used in cancer chemotherapy, the anthracycline doxorubicin specifically inhibited collagenase 1 (MMP-1) gene expression in the highly invasive and metastatic human melanoma cell line A2058. This inhibition was specific for collagenase 1 because it did not affect the expression of two other MMPs, gelatinase A (MMP-2) and gelatinase B (MMP-9). The reduction in collagenase 1 expression correlated with a decrease in the invasive ability of tumor cells through a collagen type I matrix and was independent of the cytotoxic and antiproliferative effects usually associated with this anticancer drug. The selective modulation of collagenase 1 expression by nontoxic doses of doxorubicin suggests a novel application for this chemotherapeutic agent, perhaps in combination therapy, because it decreases the invasive/metastatic potential of melanoma cells that are otherwise unaffected by this drug.
ISSN:1078-0432
1557-3265