Genomics and proteomics of bone cancer.
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abstract
Although the control of bone metastasis has been the focus of intensive investigation, relatively little is known about the molecular mechanisms that regulate or predict the process, even though widespread skeletal dissemination is an important step in the progression of many tumors. As a result, understanding the complex interactions contributing to the metastatic behavior of tumor cells is essential for the development of effective therapies. Using a state-of-the-art combination of gene expression profiling and functional annotation of human tumor cells, and surface-enhanced laser desorption/ionization time-of-flight mass spectrometry of patient serum, we have shown that changes in tumor biochemistry correlate with disease progression and help to define the aggressive tumor phenotype. Based on these approaches, it is apparent that the metastatic phenotype of tumor cells is extremely complex. The identification of the phenotype of tumor cells has benefited greatly from the application of gene expression profiling (microarray analysis). This technology has been used by many investigators to identify changes in gene expression and cytokine and growth factor elaboration (such as interleukin 8). The tumor phenotype(s) presumably also include changes in the cell surface carbohydrate profile (via altered glycosyltransferase expression) and heparan sulfate expression (via increased heparanase activity), to name but a few. These specific alterations in gene expression, identified by functional annotation of accumulated microarray data, have been validated using a variety of approaches. Collectively, the data described here suggest that each of these activities is associated with distinct aspects of the aggressive tumor cell phenotype. Collectively, the data suggest that multiple factors constitute the complex phenotype of metastatic tumor cells. In particular, the differences observed in gene expression profiles and serum protein biomarkers play a critical role in defining the mechanisms responsible for bone-specific colonization and growth of tumors in bone. Future studies will identify the mechanisms that participate in the formation of secondary tumor growths of cancers in bone.
