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The role of glycosaminoglycans in the adhesion of tumour cells to endothelium

Price, Elizabeth Ann; (1995) The role of glycosaminoglycans in the adhesion of tumour cells to endothelium. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

A fluorescence based in vitro adhesion assay has been developed to study the adhesion molecules involved in tumour cell interactions with endothelial cells, as such interactions are an important step in the metastatic cascade. The adhesion of two human tumour cell lines, the RPMI-7951 malignant melanoma and the MDA-MB-231 breast carcinoma, to human endothelial cells has been investigated. The tumour cell lines employ multiple adhesion molecules to interact with large vessel endothelial cells (HUVEC). The two lines share adhesion pathways as well as employing separate adhesion mechanisms. Both lines demonstrate calcium-and temperature- dependent adhesion to HUVEC. MDA-MB-231 cells display greater adhesion to microvessel endothelial cells than to HUVEC, while RPMI-7951 cells display no preference. B1 integrins expressed by the tumour cells and HUVEC mediate basal adhesion via unidentified heterophilic ligands. Adhesion is upregulated by treatment of HUVEC with TNFa. In the melanoma line this enhanced adhesion is due to the interaction of VLA-4 with VCAM-1 expressed by HUVEC. This mechanism is not employed during adhesion to resting HUVEC, or by MDA-MB-231 cells. Glycosaminoglycans (GAGs) on the tumour cell surfaces are anti-adhesive. The exception is hyaluronic acid (HA) expressed by the melanoma line, which acts as a ligand for CD44 on HUVEC. Endothelial cell CD44 is not involved in the adhesion of MDA-MB-231 cells. Endothelial chondroitin sulphate (CSA/C) mediates the adhesion of both tumour cell lines via unidentified ligands. Endothelial dermatan sulphate (DS) and heparan sulphate (HS) inhibit adhesion. In conclusion, RPMI-7951 employs β1 integrins, HA and VLA-4 to adhere to HUVEC. MDA-MB-231 employs β1 integrins and additional, unidentified adhesion molecules. For both lines tumour cell surface CS and HS, and HUVEC DS, are anti-adhesive. In addition, both lines interact with endothelial CS molecules via unidentified ligands.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: The role of glycosaminoglycans in the adhesion of tumour cells to endothelium
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Health and environmental sciences; Adhesion of tumour cells; Endothelium; Glycosaminoglycans
URI: https://discovery.ucl.ac.uk/id/eprint/10104264
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