The role of the IGF axis in bladder cancer progression

Bladder cancer is the 4 th most common in cancer in males and 13 th in women with a lifetime risk of 1:40 for men and 1:110 for women; the ten year survival rates are only approx. 50%. The treatments are limited: giving chemotherapy prior to surgery or radiotherapy or combining it with radiotherapy can help these treatments, but the main issue facing clinicians is that currently there is no marker available to predict which patients will respond to chemotherapy. If such a marker were identified then patients who will not benefit from chemotherapy could be offered surgery or radiotherapy immediately, avoiding delay and reducing the time available for the tumour to progress further. The IGF axis is composed of two ligands, IGF-I and –II, receptors and six high affinity IGFBPs. One of these, IGFBP-2, is a potential biomarker that we have identified from cancer cell line studies as a marker of chemo-sensitivity and of progression. We wish to investigate the role of IGFBP-2 further and to also assess the role of other members of the IGF family in bladder cancer survival, growth and metastasis. This project will use a number of techniques including cell culture of bladder cancer cell lines and co-culture of bladder cancer cells with bladder muscle cells to understand bladder cancer cell invasion into the bladder muscle. PCR and western immunoblotting, migration, invasion and colony formation assays and immunohistochemistry of tissue from patients will also be used.