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. 2012;2012:639038.
doi: 10.1155/2012/639038. Epub 2012 Feb 28.

Global Gene Expression Profiling of Human Osteosarcomas Reveals Metastasis-Associated Chemokine Pattern

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Free PMC article

Global Gene Expression Profiling of Human Osteosarcomas Reveals Metastasis-Associated Chemokine Pattern

Heidi M Namløs et al. Sarcoma. .
Free PMC article

Abstract

Global gene expression analysis was performed on a panel of 23 osteosarcoma samples of primary and metastatic origin using the Applied Biosystems Gene Expression Array System. When comparing the primary tumours with the metastases, we found a significantly increased expression of genes involved in immunological processes, for example coding for cytokines and chemokines, in the metastatic samples. In addition, a comparison of the gene expression in primary samples from patients with or without metastases demonstrated that patients who later developed metastases had high expression of the chemokine (C-X-C motif) receptor 4 (CXCR4), similar to the metastatic samples, suggesting that these signal molecules play an important role in promoting metastasis. Increased knowledge of mechanisms and interactions between specified molecular signalling pathways in osteosarcomas could lead to a more rational strategy for development of targeted therapy.

Figures

Figure 1
Figure 1
Hierarchical clustering of all tumours based on the top-210 significant genes differentially expressed between metastases and primary tumours, identified by SAM analysis. Samples coloured in red, metastases; lilac, primary samples from patients who later developed metastases; green, primary samples from patients who did not develop metastases blue, clinical information on metastases not available. Gene cluster coloured in blue, CXCL1, -2, -3, IL6, and LOC131873; green, EGR1, -2, FOSB, FOS, and JUNB; red, surfactant genes. Red, increased gene expression; green, decreased gene expression. The cluster was made using average linkage and Pearson's correlation.
Figure 2
Figure 2
Hierarchical clustering of all primary tumours based on the top-20 significant genes differentially expressed between primary samples from patients who developed metastases and those who did not, identified by SAM analysis (one primary tumour with no clinical information on metastases was excluded). Samples coloured in lilac, primary samples from patients who later developed metastases; green, primary samples from patients who did not develop metastases. Red, increased gene expression; green, decreased gene expression. The cluster was made using average linkage and Pearson's correlation.
Figure 3
Figure 3
Relative CXCR4 expression in primary tumours from patients who did or did not develop metastases and in metastatic samples (one primary tumour with no clinical information on metastases was excluded) based on (a) microarray data and (b) quantitative real-time RT-PCR data. For the quantitative real-time RT-PCR data, the expression levels have been normalised to the average expression of three housekeeping genes (18S, B2M and TBP) and compared to the average expression of two normal bone samples. The average expression level in each sample group is indicated with a black bar. NA, not available.

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