期刊
MELANOMA RESEARCH
卷 23, 期 4, 页码 243-253出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CMR.0b013e3283625498
关键词
caspase-3; invasion; melanoma; migration; vasculogenic mimicry
资金
- key project of the National Natural Science Foundation of China [81230050]
- Project of the National Natural Science Foundation of China [81172046, 81173091]
- International Cooperation Project of China and Sweden [09ZCZDSF04400]
- Research Fund for the Doctoral Program of Higher Education [20111202110010]
- 973 Program from the Ministry of Science and Technology of China [2009CB918903]
Melanoma is the least common but most serious form of skin cancer. The leading cause of death in melanoma patients is widespread metastasis caused by increased cell motility and a rich blood supply for tumor cells. A unique form of microcirculation called vasculogenic mimicry, which efficiently supplies blood to tumor cells, has been reported recently. Apoptosis-related protein performs a nonapoptotic function to promote migration and invasion of tumor cells. This study focuses on the nonapoptotic role of caspase-3 in melanoma and its effects on the migration, invasion, and vasculogenic mimicry formation of melanoma cells. Human melanoma samples were used to detect active caspase-3 expression and determine its relationship with clinicopathologic parameters. In addition, a human melanoma A375 cell line was used to determine the role of caspase-3 in migration and invasion using z-DEVD-fmk, a selective caspase-3 inhibitor, to inhibit caspase-3 activity. The findings suggest that active caspase-3 is expressed in nonapoptotic melanoma cells and is related to metastasis and vasculogenic mimicry formation in patients with melanoma. Low doses of caspase-3 inhibitor reduced caspase-3 activity without affecting cell apoptosis. Inhibition of caspase-3 activity using low-dose z-DEVD-fmk decreased the migration, invasion, and vasculogenic mimicry formation of melanoma cells in vitro. Similarly, downregulation of caspase-3 by specific small interfering RNA also inhibited the migratory, invasive, and tube-forming potential of melanoma cells. The caspase-3-mediated promotion of melanoma cell motility may be because of the cleavage of matrix metalloproteinase-2. Melanoma Res 23: 243-253 (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
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