Poster Presentation 14th International Biennial Conference on Metastasis Research 2012

Tetraspanins as metastatic regulators of prostate cancer (#153)

Ben T Copeland 1 , Matthew J Bowman 1 , Claude Boucheix 2 , Ashman K Leonie 1
  1. School of Biomedical Sciences and Pharmacy, University of Newcastle and Cancer Research Program, Hunter Medical Research Institute, Newcastle, N.S.W, Australia
  2. INSERM U602, Hôpital Paul Brousse, Villejuif, Cedex, France

Prostate cancer accounts for the second highest cause of cancer related deaths in men in most western countries, including Australia and the United States. The majority of deaths are attributed to late stage metastatic forms of the disease. Tetraspanins are integral membrane bound proteins that associate with motility related molecules such as integrins. Experimental studies have indicated tetraspanins may be important regulators of tumour invasion and metastasis. High expression levels of the tetraspanin CD9 have been linked to good prognosis, while in contrast increased expression of the tetraspanin CD151 has been associated with poor outcomes. In this study, for the first time the effects of knocking-out the pro- and anti-tumorigenic/metastatic tetraspanins on development of prostate cancer have been evaluated in a spontaneously developing model of prostate cancer.

The Cd9 and Cd151 knock-out mouse models were independently crossed onto the TRansgenic Adenocarcinoma of Mouse Prostate (TRAMP) mouse model. Development of primary prostate tumours were not affected by knocking out either Cd9 or Cd151. Knocking out the Cd9 gene resulted in a significant increase of metastatic lesions, number of foci and total area of metastatic lesions, to the liver. While knocking out the Cd151 gene resulted in a significant decrease of metastatic lesions, number of metastatic foci and total area of metastatic lesions, to the lungs.

In summary, in the TRAMP model, tetraspanins CD9 and CD151 have no significant effect on the development of primary prostate tumours. CD9 has a significant anti-metastatic effect while conversely CD151 has a significant pro-metastatic effect. CD9 and CD151 may prove to be therapeutic targets that benefit prostate cancer patients.