Morphine-induced alterations of tumor cell activity, and tumor cell-endothelial cell interactions: The role of nitric oxide.
Item
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Title
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Morphine-induced alterations of tumor cell activity, and tumor cell-endothelial cell interactions: The role of nitric oxide.
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Identifier
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AAI3063814
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identifier
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3063814
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Creator
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Chang, Jungshan.
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Contributor
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Adviser: Jeanne Szalay
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Date
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2002
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Cell | Health Sciences, Oncology
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Abstract
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We examine the effects of morphine on THP-1 human monocytic leukemia cells, on B16F10 murine melanoma cells, and on the vascular endothelium of mouse aortic rings. Morphine had profound effects on both tumor cell lines. Morphine reduced cell proliferation and survival in both cell lines, and cell death was not mediated by apoptosis. Invasion of the TC across a fibronectin barrier was inhibited by morphine in both cell lines. This inhibition was only partially prevented by pre-treatment of THP-1 with either naloxone, or L-NAME. However, the inhibition of B16F10 cell invasion was completely abrogated by pre-treatment of these cells with naloxone, but unaffected by L-NAME. Thus, in THP-1 cells, morphine affected invasion by both a NO-dependent and NO-independent mechanism; while in melanoma cells, morphine's effect appeared to be mediated solely by a NOS-independent, but opioid receptor-dependent mechanism. Morphine affected cell shape and actin polymerization in the THP-1 cell line, but had little or no effect on the B16F10. Morphine affected adhesion of B16F10 cells to aortic rings, and this effect was dependent on time after morphine treatment. Two hours after pre-treatment of aortic rings with morphine, adhesion was significantly increased when compared with saline treated aorta. 48 hours after pre-treatment of rings with morphine, adhesion was significantly decreased in both control and drug treated groups, but significantly fewer cells were seen in the morphine treated group than in the controls. The altered adhesion seen at both 2 and 48 hours was mu3 and EC-NOS dependent. Experiments with RGD peptide suggest that B16F10 adhesion to the aortic endothelium is mediated by melanoma cell integrins, and that morphine treatment of the vascular endothelium impacts subsequent adhesion of endothelial cells to melanoma cell integrins. In summary, the results of this thesis demonstrate that morphine can directly affect tumor cell proliferation and viability, invasion, and tumor-endothelial cell adhesion. Our studies provide new and important information by demonstrating that morphine may act directly on tumor cells in either a NO-dependent or NO-independent manner, and on endothelial cells in a NO dependent manner modulating properties of these cells that are capable of profoundly altering metastatic potential.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
