Article

CD24 affects CXCR4 function in pre-B lymphocytes and breast carcinoma cells.

Tumor Immunology Programme, D010, German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Journal of Cell Science (impact factor: 6.11). 02/2006; 119(Pt 2):314-25. DOI:10.1242/jcs.02741 pp.314-25
Source: PubMed

ABSTRACT CD24 is a small, heavily glycosylated cell-surface protein which is linked to the membrane via a glycosyl-phosphatidylinositol (GPI-) anchor and therefore localizes in lipid rafts. CD24 is widely used as a cell-lineage marker for hematopoietic cells. CD24 is also expressed on a variety of human carcinomas, including epithelial ovarian, breast, prostate, colon and lung cancer and has been linked to poor prognosis. Except for its role as a ligand for P-selectin on carcinoma and myeloid cells, a specific function for CD24 has not been determined. Here we show that CD24 affects the function of the chemokine receptor CXCR4. Using isolated CD19-positive bone marrow B cells from CD24-knockout mice and CD24-/- pre-B lymphocytic cell lines, we demonstrate that CD24 expression reduces SDF-1-mediated cell migration and signalling via CXCR4. We observed that the loss of CD24 augmented cellular cholesterol levels and enhanced CXCR4 lipid raft association. Altered chemotactic migration and raft residence was also observed in MDA-MB-231 breast cancer cells expressing high and low levels of CD24 and CXCR4 receptor. MDA-MB-231 cells expressing low levels of CD24 also showed enhanced tumour formation in NOD/SCID mice compared with cells overexpressing CD24. These results demonstrate a novel role for CD24 as a regulator of CXCR4 function that could be relevant for breast cancer growth and metastasis.

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Keywords

Altered chemotactic migration
 
breast cancer growth
 
CD19-positive bone marrow B cells
 
CD24 augmented cellular cholesterol levels
 
CD24-/- pre-B lymphocytic cell lines
 
cells overexpressing CD24
 
chemokine receptor CXCR4
 
CXCR4 function
 
CXCR4 lipid raft association
 
CXCR4 receptor
 
epithelial ovarian
 
glycosylated cell-surface protein
 
lipid rafts
 
lung cancer
 
MDA-MB-231 breast cancer cells
 
MDA-MB-231 cells
 
raft residence
 
SDF-1-mediated cell migration
 
specific function
 
tumour formation
 

Heidi Schabath