Deciphering the molecular basis of cancer is critical for developing novel 
diagnostic and therapeutic strategies. To better understand the early molecular 
events involving osteogenic sarcoma (OGS), we have initiated a program to 
identify potential tumor suppressor genes. Expression profiling of total RNA 
from ten normal bone cell lines and eleven OGS-derived cell lines by microarray 
showed 135-fold lower expression of FRZB/sFRP3 mRNA in OGS cells compared to 
bone cells; this down-regulation of Frzb/sFRP3 mRNA expression was found to be 
serum-independent. Subsequently, fourteen OGS biopsy specimens showed nine-fold 
down-regulation of Frzb/sFRP3 mRNA expression compared to expression in eight 
normal bone specimens as determined by microarray. FRZB /sFRP3 protein level was 
also found to be at a very low level in 4/4 OGS cell lines examined. 
Quantitation by RT-PCR indicated approximately 70% and approximately 90% loss of 
Frzb/sFRP3 mRNA expression in OGS biopsy specimens and OGS-derived cell lines 
respectively, compared to expression in bone (p<0.0001). Hybridization 
experiments of a cDNA microarray containing paired normal and tumor specimens 
from nineteen different organs did not show any significant difference in the 
level of Frzb/sFRP3 mRNA expression between the normal and the corresponding 
tumor tissues. Exogenous expression of FRZB/sFRP3 mRNA in two OGS-derived cell 
lines lacking endogenous expression of the mRNA produced abundant mRNA from the 
exogenous gene, eliminating degradation as a possibility for very low level of 
FRZB/sFRP3 mRNA in OGS specimens. Results from PCR-based experiments suggest 
that the FRZB/sFRP3 gene is not deleted in OGS cell lines, however, karyotyping 
shows gross abnormalities involving chromosome 2 (location of the FRZB gene) in 
five of twelve OGS-derived cell lines. Together, these data suggest a 
tumor-suppressive potential for FRZB/sFRP3 in OGS.