The Role of CXCL12 (SDF-1)/CXCR4 in Pathological Angiogenesis and Osteolytic Bone Disease in Multiple Myeloma

Funding Activity

Website
http://purl.org/au-research/grants/nhmrc/453495

Funding Status
Closed

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Funded Activity Summary

Multiple myeloma (MM) is the second most common haematological (or blood) cancer in western countries and is unique amongst blood cancers in its capacity to destroy the skeleton. MM is a cancer of plasma cells, which in their normal non-cancerous form, reside in lymph nodes and produce antibodies against infectious agents. When they become cancerous, they migrate or home to congenial sites within the bone marrow (BM). This directed movement or homing occurs under the influence of a chemokine molecule called CXCL12 which acts as a calling card for plasma cells to leave the lymph node and migrate to the BM. Once within the BM, the cells rapidly grow in response to BM-derived growth factors. This rapid growth causes a depletion in oxygen availability within the tumour and it becomes hypoxic. In response to this hypoxia, the tumour expresses a gene called hypoxia-inducible factor-1 (HIF-1) which regulates the expression of many proteins, including the chemokine CXCL12. Our studies show that the abnormal expression of CXCL12 by the plasma cells acts to promote blood vessel formation within the tumour, which in turn leads to greater tumour growth. In addition, our studies suggest that abnormal CXCL12 expression also promotes the recruitment and activation of large numbers of osteoclast (OC) precursors form the peripheral blood. OC are cells which normally remove unwanted or damaged bone. This proposal will study the interplay between HIF and CXCL12 in the establishment and development of MM and the associated bone destruction.

Funded Activity Details

Start Date: 01-01-2007

End Date: 01-01-2009

Funding Scheme: NHMRC Project Grants

Funding Amount: $665,896.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Haematology

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

aberrant bone remodelling | cancer cell-mediated osteolysis | chemokine activation of osteoclast function | haematological cancer which is metastatic to bone | haematological malignancy | orthopaedic osteolysis | osteolytic bone disease | pathological angiogenesis

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