The role of fibroblast growth factor-9 in malignant mesothelioma

[Truncated abstract] Background: Malignant mesothelioma (MM) is a cancer with no cure and its global incidence continues to rise. Identifying the key molecules governing the pathogenesis of MM is urgently needed. Such molecules can potentially provide better understanding of the disease pathology, unveil therapeutic targets and may have diagnostic or prognostic relevance. Fibroblast growth factor-9 (FGF-9) was the leading candidate gene in a pilot global gene profiling study of our laboratory using prospectively-collected human thoracoscopic biopsies. The finding was validated in a second cohort. FGF-9 expression was 17- and 35-fold higher in MM over controls (metastatic pleural carcinomas and benign pleuritis) in those studies. This thesis followed on the data to explore the biological significance of FGF-9 in MM. Hypothesis: I hypothesize that: FGF-9 plays a vital role in MM development including proliferation and invasion; Antagonising FGF-9 activity retards MM growth; FGF-9 can aid diagnosis of MM; Mutations in the FGF-9 and/or its receptors cause aberrant FGF-9 signalling in MM. Results: I demonstrated the presence of FGF-9 protein in all 10 human and murine MM cell lines tested. Using tissue-array of human fluid cells and pleural tissues, FGF-9 immunostaining was significantly stronger in MM (n=121) and metastatic adenocarcinoma (n=29) over benign controls (n=35), chi-square 82.8, df=2, p