Mechanisms of CD44v2-10-mediated tumour metastasis.

Funding Activity

Website
http://purl.org/au-research/grants/nhmrc/252863

Funding Status
Closed

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Funded Activity Summary

Cancer metastasis remains the principal cause of treatment failure in malignant disease. Current therapies for metastases are generally non-specific, and can cause considerable systemic toxicity. The ideal target for metastasis therapy would be expressed by a broad range of tumours, but be restricted in expression in normal tissues. CD44 is a family of widely expressed cell-surface adhesion molecules and its members are implicated in a variety of physiological and pathological processes, including tumour progression and metastasis. CD44 has considerable molecular diversity and its broad range of known biological activities suggests that multiple domains in the molecule may confer different biological functions. The core CD44 molecule, termed CD44s, is the most commonly expressed CD44 molecule. CD44 variants (termed CD44v) are much more restricted in their expression in normal tissues, and hence may make specific targets for anti-metastasis therapy. We have shown that CD44 variants are expressed by colorectal tumours from the earliest stages of tumour development, and that theses variants are found to be expressed by colorectal hepatic metastases. We targeted two key domains in the variants and found that by inhibiting expression in these domains we showed complete abrogation of metastasis, and of primary tumour growth in mice. Hence these domains in the CD44 molecule are directly involved in cancer spread. We propose to investigate the mechanisms by which specificdomains in the CD44 variants actually cause tumour spread. Understanding of the various mechanisms involved in tumour spread, and targeting the functions of the domains has enormous potential as a therapeutic target.

Funded Activity Details

Start Date: 01-01-2003

End Date: 01-01-2005

Funding Scheme: NHMRC Project Grants

Funding Amount: $441,000.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Surgery

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

CD44 | cancer | cell adhesion | cell signalling | metastasis | surgery | therapy

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