Elevated expression of CXC chemokines in pediatric osteosarcoma patients

Abstract

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. Cancer 2011;117:207-17.

Strong expression of CXCL12 is associated with a favorable outcome in osteosarcoma

“…10,21,22 CXCL12 has only once been investigated immunohistochemically in a larger series of OSs and was found to be positive in just 4/113 (4%) of cases. 23 In contrast, we detected strong and constant immunoreactivity in 158/204 (78%) of cases in our series. Li et al 20 applied the same antibody used in our study, and although they did not state what kind of decalcification was performed or which cellular compartments were evaluated, this marked difference cannot be explained unequivocally.…”

Biomarkers of Osteosarcoma, Chondrosarcoma, and Ewing Sarcoma

“…The chemokine, molecules involved in tumor genesis, have been studied by Li et al (2011). The author observed an increase in serum levels in patients with osteosarcoma, particularly CXCL4 and CXCL, and affirmed that the marker play a role in clinical results and new studies are needed for the treatment (Li et al, 2011).…”

Bone Formation Deregulations Are the Oncogenesis Keys in Osteosarcomas

“…They can be also involved in various cellular processes such as skeletal rearrangements, cell migration and cell adhesion (Fernandez et al, 2002). In OS, the circulating CXC chemokines (CXCL4, CXCL6 and CXCL12) seem to present higher concentrations (Li et al, 2011), correlated with a worst outcome in patients. They also stimulate the specific angiogenic and hypoxic signaling pathways, which are favoring the metastatic spread.…”