Autocrine tumour growth factors
As described in Project 8, many tumours secrete a molecule which can act to stimulate growth of the tumour in a so-called autocrine loop. One such growth factor is a genetic variant of the pregnancy hormone, human chorionic gonadotrophin (hCG), which we have recognised uses a DNA sequence not expressed by normal cells. We will investigate the possibility that the presence of the hCG variant in the serum DNA of cancer patients and/or the abnormal protein which it encodes, can provide useful prognostic indicators and/or biomarkers to monitor therapy.
c-Met receptor is a surface marker of many tumours but is particularly related to cancer stem cells from which the tumour mass differentiates (compare Project 1). The cells are stimulated when the c-Met binds its circulating ligand, hepatocyte growth factor (HGF). We will examine the possibility that tumour cells (cell lines initially) express c-Met and if so, whether they secrete HGF and/or are stimulated by this growth factor (we should apply this also to the stem cell progeny produced in Project 1).
Like the hCG experiments suggested above, the presence of HGF and/or c-Met in serum should be studied along with hCG and other serum tumour biomarkers as a possible array for diagnosis and/or therapy monitoring. Look also for possible autoantibodies and abnormal c-Met DNA.
1. To find new serum biomarkers as prognostic indicators of disease and as monitors of therapy.
2. Look for possible new c-Met/HGF autocrine loop.
3. Examine any surface phenotypic changes induced by autocrine stimulation.
Dr. S. Butler
Dr. S. Wen Scientific support
Dr. L. Ghali Scientific support
(Poznan) Serum DNA
Research Assistant Cell and biomarker studies
Dr. P. Cohen (Histopath., Imperial)
Supply clinical materials
Prof. I. Cree (Warwick)