Autotaxin expression in bladder and renal cancer

Anderson, Jane Ann (2016). Autotaxin expression in bladder and renal cancer. University of Birmingham. M.D.

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Abstract

Autotaxin is an extracellular enzyme that generates lysophosphatidic acid (LPA). LPA binds up to six different cell surface G protein-coupled receptors to initiate signaling resulting in cell survival, invasion and angiogenesis. For this reason autotaxin has emerged as a therapeutic target in several different malignancies.

I have used immunohistochemistry to explore the expression of autotaxin and its correlation with clinico-pathological variables in bladder and renal cancer.

I show that in bladder cancer, tumours from patients with muscle invasive disease were significantly more likely to show strong autotaxin expression than were those tumours from patients without evidence of muscle involvement (p=0.009). This observation is not only consistent with the known functions of autotaxin/LPA in promoting tumour invasion, but suggests that the potential use autotaxin inhibitors in preventing bladder cancer progression warrants further investigation.

Although I failed to detect autotaxin expression in the tumour cells of patients with renal cancer, I did observe high-level expression of autotaxin on the tumour-associated vasculature, which in many cases was not apparent in blood vessels of matched normal renal tissues. This points to an important role for autotaxin in renal cancer-associated angiogenesis and suggests a potential role for autotaxin inhibition as an anti-angiogenesis therapy.

Type of Work:

Thesis (Higher Doctorates > M.D.)

Award Type:

Higher Doctorates > M.D.

Supervisor(s):