Early investigations of the urokinase type plasminogen activator (uPA) receptor (uPAR) and
its ligand, uPA, were limited to their role in degradation of the extracellular matrix (ECM)
and invasion. Emerging evidence revealed that uPAR and its relationship with uPA and/or
transmembrane proteins, such as the integrins, affects cell-ECM adhesion events and
proliferation. These events are tightly coordinated and essential for epithelial tissue
development. However, unregulated expression of molecules involved in cell adhesion and
proliferation plays a significant role in tumour development and metastasis. The
overexpression of uPAR is linked to several cancer types, including human oesophageal
squamous cell carcinoma (HOSCC). This study examines the contribution of uPAR, and its
communication with extracellular components, to cell-ECM adhesion and/or proliferation of
HOSCC cells. The confirmation of the uPAR and 1-integrin expression as well as uPA
secretion in the HOSCC cells lines, established these lines as excellent models for further
investigation. In all the HOSCC cell lines, uPAR associated with integrin-linked kinase, a
scaffolding protein in cell-ECM adhesion events. Data presented in this investigation
confirmed that the interaction of uPAR with uPA or 1-integrin contributed to adhesion of the
HOSCC cell lines on collagen type I and vitronectin. It was clearly established that uPAR also
played a part in the proliferation of all the HOSCC cell lines. The uPAR role in proliferation
is influenced by: a) The absence or presence of collagen type I or vitronectin substrates; b)
The activation of uPAR by endogenous uPA; c) The uPAR/1-integrin interaction; d) the
presence of transforming growth factor and epidermal growth factor. In the current study, it
was successfully demonstrated that uPAR, and its relationship with the ECM and growth
factors, contributes to adhesion and proliferation during the progression of HOSCC. This
gives uPAR a considerable value as a therapeutic target for HOSCC.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/11830 |
| Date | 27 August 2012 |
| Creators | Dahan, Yael-Leah |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
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