Elevated expression of CXC chemokines in pediatric osteosarcoma patients

Yiting Li, Ricardo Flores, Alexander Yu, M. Fatih Okcu, Jeffrey Murray, Murali Chintagumpala, John Hicks, Ching C. Lau, Tsz Kwong Man

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)207-217
Number of pages11
JournalCancer
Volume117
Issue number1
DOIs
StatePublished - Jan 1 2011

Keywords

  • antibody microarray
  • biomarkers
  • cell proliferation
  • CXC chemokines
  • osteosarcoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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