PROTEASE SUBSTRATES - Molecular evolution of protease substrates involved in carcinogenesis by in vivo selection of retroviral display libraries (LIFE QUALITY) (2000-02-01 - 2004-01-31) (»add to infobox)

Simon KERR, Alfredo GARCIA IGLESLAS, Claude GRISCELLI, Klaus CICHUTEK

CAMBRIDGE DRUG DISCOVERY HOLDINGS LIMITED (UK401 - Cambridgeshire) (Great Britain), HOSPITAL UNIVERSITARIO CLINICA PUERTA DE HIERRO (ES300 - Madrid) (Spain), INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM) (FR716 - Rhône) (France), PAUL-EHRLICH-INSTITUT (BUNDESAMT FUER SERA UND IMPFSTOFFE) (DE716 - Darmstadt-Dieburg) (Germany)

The transition from benign to malignant phenotype involves the protease-mediated breakdown of basement membrane surrounding a primary cancer, allowing cells to escape and initiate metastatic tumours. The complex proteolytic machinery responsible for this process is supplied and regulated by the invading cells and the stromal cells. This proposal describes highly innovative strategies based on molecular evolution of retrovirus peptide display libraries to determine the substrate specificities of these proteases under physiological conditions, to generate programmable retroviral targeting vectors selective for sites of tumour invasion and to clone novel tumour associated proteases. The project will facilitate the improvement of molecular evolution technologies, the understanding of tumour invasion and the development of anti-cancer therapeutics.

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