Blocking a6 integrin cleavage as a therapeutic target for prostate cancer bone metastases

Project Information

INTEBLOCK

Grant agreement ID: 36567

Project closed

Start date 1 April 2006

End date 31 March 2008

Funded under

• Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006

Total cost No data

EU contribution € 80 000,00

Coordinated by

UNIVERISTY OF CYPRUS
Cyprus

Objective

Prostate cancer affects people all over the world. The most frequent site of prostate cancer metastasis is the bone and once it has metastasised it is incurable and extremely painful. The goal of this proposal is to develop new therapeutic tools for palliative care for bone metastases. Our model states that the high levels of uPA in the bone induce cleavage of the a6 integrin in prostate cancer cells, leading to the activation of other integrins (such as a2, a3 and av) to allow for migration and homing on the bone matrix. In this proposal, we will investigate whether the a6 integrin cleavage by uPA controls cell adhesion by integrins other than the a6 integrin, a process referred to as "integrin switching".

In addition, we will investigate whether the a6 integrin cleavage by uPA controls migration through focal adhesion signalling. First, we will test the hypothesis that blocking the cleavage of the a6 integrin will reduce osteoblast conditioned media (OBCM) induced adhesion of prostate cancer cells on b one matrix. We will test this by using a peptide and an antibody designed to prevent a6 integrin cleavage and we will also perform transfections of an uncleavable a6 integrin mutant in the PC3 prostate cancer cell line. We will evaluate changes in adhesio n on different substrates (collagen, vitronectin and osteopontin) using cell adhesion assays. Second, we will test the hypothesis that blocking the cleavage (using a peptide, an antibody and transfections) of the a6 integrin will reduce the phosphorylation levels of FAK, Pax and p130CAS upon OBCM stimulation.

Third, using the peptide, the antibody and the transfections in the PC3 cell line, we will investigate the role of the a6 integrin cleavage by uPA in cell migration and invasion upon OBCM stimulation . Migration will be measured using the Cell Sedimentation Manifold (CSM), and the scratch assay, and invasion using the Boyden chamber method.

Fields of science

• medical and health sciences › clinical medicine › oncology › prostate cancer
• natural sciences › earth and related environmental sciences › geology › sedimentology
• natural sciences › biological sciences › biochemistry › biomolecules
• natural sciences › biological sciences › cell biology
• natural sciences › biological sciences › developmental biology

Programme(s)

• FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006

Topic(s)

• MOBILITY-4.2 - Marie Curie International Reintegration Grants (IRG)

Call for proposal

FP6-2004-MOBILITY-12
See other projects for this call

Funding Scheme

IRG - Marie Curie actions-International re-integration grants

Coordinator

UNIVERISTY OF CYPRUS

• EU contribution: No data
• Address: Kallipoleos 75 ; NICOSIA ; Cyprus
• Total cost: No data