Elevated expression of CXC chemokines in pediatric osteosarcoma patients.
BACKGROUND
Osteosarcoma is the most common malignant bone tumor in children. Despite the advent of chemotherapy, the survival of osteosarcoma patients has not been significantly improved recently. Chemokines are a group of signaling molecules that have been implicated in tumorigenesis and metastasis.


METHODS
The authors used an antibody microarray to identify chemokines that were elevated in the plasma samples of osteosarcoma patients. The results were validated using enzyme-linked immunosorbent assays on an independent set of samples. The tumor expressions of 3 chemokines were examined in 2 sets of osteosarcoma tissue arrays. The authors also evaluated the proliferative effect of the chemokines in 4 osteosarcoma cell lines.


RESULTS
The authors found that the plasma levels of CXCL4, CXCL6, and CXCL12 in the osteosarcoma patients were significantly higher than those in the controls, and the results were validated by an independent osteosarcoma cohort (P < .05). However, CXCL4 (100%) and CXCL6 (91%) were frequently expressed in osteosarcoma, whereas CXCL12 was only expressed in 4%. Survival analysis further showed that higher circulating levels of CXCL4 and CXCL6, but not CXCL12, were associated with a poorer outcome of osteosarcoma patients. Addition of exogenous chemokines significantly promoted the growth of different osteosarcoma cells (P < .05).


CONCLUSIONS
The results demonstrate that CXCL4 and CXCL6 are frequently expressed in osteosarcoma, and that the plasma levels of these 2 chemokines are associated with patient outcomes. Further study of these circulating chemokines may provide a promising approach for prognostication of osteosarcoma. Targeting these chemokines or their receptors may also lead to a novel therapeutic invention.
Li
Yiting
Y
Texas Children's Cancer Center, Texas Children's Hospital, Houston, Texas; Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
Flores
Ricardo
R
Yu
Alexander
A
Okcu
M Fatih
MF
Murray
Jeffrey
J
Chintagumpala
Murali
M
Hicks
John
J
Lau
Ching C
CC
Man
Tsz-Kwong
TK
D000293:Adolescent; D014408:Biomarkers, Tumor; D001859:Bone Neoplasms / Q000097:blood* / Q000401:mortality; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000097:blood; D054427:Chemokine CXCL6 / Q000097:blood; D019743:Chemokines, CXC / Q000097:blood*; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D012516:Osteosarcoma / Q000097:blood* / Q000401:mortality; D010978:Platelet Factor 4 / Q000097:blood; D015203:Reproducibility of Results; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D054377:Chemokine CXCL12; D054427:Chemokine CXCL6; D019743:Chemokines, CXC; D010978:Platelet Factor 4
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