Messenger RNA expression levels of CXCR4 correlate with metastatic behavior and outcome in patients with osteosarcoma.
OBJECTIVE
To determine if osteosarcoma cells express chemokine receptors and if their presence or absence relates to clinical features.


METHODS
Using fluorescent quantitative real-time PCR, the pattern of 17 chemokine receptors in 3 osteosarcoma cell lines and 68 osteosarcoma patient samples was analyzed.


RESULTS
The expression of the chemokine receptors was generally low among the cell lines. In the high-grade osteosarcoma patient samples (n = 47), CXCR4 was the most commonly expressed (63%) and its expression level was inversely correlated to overall survival (P < 0.0001), event-free survival (P < 0.001), and metastasis-free survival (MFS; P = 0.002). There was also a correlation between the expression level of CXCR4 and the presence of metastasis at diagnosis (P = 0.002). CCR7 was expressed in 43% of the samples and its expression level was inversely correlated with overall survival (P = 0.03) and MFS (P = 0.007). CCR10 mRNA expression level was inversely correlated with MFS (P = 0.009). There was no association between the expression of CXCR4, CCR7, and CCR10. Of the 26 samples studied for stromal cell-derived factor-1 expression, 77% expressed it, but there was no correlation with the clinical variables or CXCR4 expression. Multivariate analysis revealed that mRNA expression level of CXCR4 was the only significant variable for overall survival (P = 0.0006), event-free survival (P = 0.004), and MFS (P = 0.025).


CONCLUSIONS
These data suggest that CXCR4 could be useful as a prognostic factor and as a predictor of potential metastatic development in osteosarcoma. If further studies confirm that it is relevant to metastases in this disease, it could represent a new therapeutic target.
Laverdiere
Caroline
C
Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Hoang
Bang H
BH
Yang
Rui
R
Sowers
Rebecca
R
Qin
Jing
J
Meyers
Paul A
PA
Huvos
Andrew G
AG
Healey
John H
JH
Gorlick
Richard
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D012516:Osteosarcoma / Q000235:genetics / Q000473:pathology*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D054447:Receptors, CCR10; D054400:Receptors, CCR7; D019718:Receptors, CXCR4 / Q000235:genetics*; D019707:Receptors, Chemokine / Q000235:genetics; D016019:Survival Analysis
C515706:CCR10 protein, human; C515370:CCR7 protein, human; D012333:RNA, Messenger; D054447:Receptors, CCR10; D054400:Receptors, CCR7; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine