Adhesion of murine RAW117 lymphoma cells to hepatic sinusoidal endothelial cells: Study of surface molecule interactions under flow and effect of cyclooxygenase and lipoxygenase inhibitors

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dc.contributor.advisorMcIntire, Larry V.en_US
dc.creatorPapadimitriou, Minas N. B.en_US
dc.date.accessioned2009-06-04T08:49:49Zen_US
dc.date.available2009-06-04T08:49:49Zen_US
dc.date.issued2000en_US
dc.description.abstractAdhesion of malignant tumor cells under flow conditions to the endothelial monolayer lining the interior of the blood vessels is an important step in the metastatic cascade. This project examined the adhesive interactions of murine RAW117 large-cell lymphoma cells to murine hepatic sinusoidal endothelial cells (HSE). Flow cytometric analysis demonstrated constitutive-expression of VCAM-1, ICAM-1, PECAM-1 and beta1 integrin subunit on the surface of both HSE and RAW117 cells. Additionally, alpha4 and beta 7 integrin subunits and MAdCAM-1 were present on the RAW117 cell surface. The dynamic adhesion assay used employs a parallel-plate flow chamber coupled with video microscopy and digital image processing. It is capable of distinguishing initial attachment from adhesion stabilization. Using monoclonal antibodies to block the surface molecules mentioned above, we determined that an interaction of integrin alpha4beta1 on RAW117 cells with liver endothelial VCAM-1 occurs during the early stages of the adhesion process and may be important in liver metastasis. The second part of this project focused on the potential role of the cyclooxygenase (COX) pathway in the adhesive interactions of the cells studied. COX-1 isoform was detected in unstimulated RAW117 cells. Blocking it with COX inhibitors such as indomethacin, aspirin, sulindac and piroxicam resulted in increase in adhesion under static conditions. However, when lipoxygenase (LOX) inhibitors (such as ETI, NDGA and Esculetin) were used either alone or in combination with COX inhibitors, there was a significant decrease in adhesion. This observation suggested an involvement of the LOX pathway in the adhesion process. COX-2 isoform was detected in unstimulated HSE and was upregulated after stimulation with TNF-alpha. Blocking it in unstimulated HSE resulted in an increase in adhesion of RAW117. However, in the case of TNF-alpha stimulated HSE, NS-398 (a COX-2 specific inhibitor) caused a significant decrease in adhesion, indicating a potential role for COX-2 in the adhesion of RAW117 to stimulated HSE.en_US
dc.format.extent142 p.en_US
dc.format.mimetypeapplication/pdfen_US
dc.identifier.callnoTHESIS CH.E. 2000 PAPADIMITRIOUen_US
dc.identifier.citationPapadimitriou, Minas N. B.. "Adhesion of murine RAW117 lymphoma cells to hepatic sinusoidal endothelial cells: Study of surface molecule interactions under flow and effect of cyclooxygenase and lipoxygenase inhibitors." (2000) Diss., Rice University. <a href="https://hdl.handle.net/1911/19545">https://hdl.handle.net/1911/19545</a>.en_US
dc.identifier.urihttps://hdl.handle.net/1911/19545en_US
dc.language.isoengen_US
dc.rightsCopyright is held by the author, unless otherwise indicated. Permission to reuse, publish, or reproduce the work beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.subjectCell biologyen_US
dc.subjectOncologyen_US
dc.subjectBiologyen_US
dc.subjectHealth sciencesen_US
dc.titleAdhesion of murine RAW117 lymphoma cells to hepatic sinusoidal endothelial cells: Study of surface molecule interactions under flow and effect of cyclooxygenase and lipoxygenase inhibitorsen_US
dc.typeThesisen_US
dc.type.materialTexten_US
thesis.degree.departmentChemical Engineeringen_US
thesis.degree.disciplineEngineeringen_US
thesis.degree.grantorRice Universityen_US
thesis.degree.levelDoctoralen_US
thesis.degree.nameDoctor of Philosophyen_US
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