Discovery of Tumor Metastasis Related Genes

Ultimately, conquering metastatic disease will likely derive from a more thorough characterization of the genes expressed during each step of metastasis. Transcriptional and functional analysis of metastatic gene products may provide new insights into the molecular mechanisms underlying the process of metastasis and identify potential targets for therapeutic intervention.

Molecular technologic advances have made it possible to discover genes that are differentially expressed between normal physiologic and aberrant pathologic states. Two of the more versatile techniques that permit identification of variably expressed genes are differential display and microarray analysis.207 Differential display employs reverse transcription and the polymerase chain reaction using mRNA derived from different cellular states, allowing, for example, the identification of genes that are expressed during the process of metastasis and not expressed during nonpathologic states. Another technique used to examine differential gene expression, microarray analysis, characterizes gene expression based on the relative hybridization of reversed transcribed gene products to a prefabricated, nucleic acid-containing matrix. Demonstrating their power and utility, these techniques have been used to discover metastasis suppressor genes208 and metastatic molecular signatures.209-211

The endeavor to discover metastasis-related genes has inspired innovative investigative approaches including the use of phage display technology. Ngaiza and colleagues212 employed this technique to identify colon cancer genes mediating metastasis to the liver. The gene products from a highly metastatic colon cancer cell line were expressed on the surface of the phage. Genes involved directly in the process of liver metastasis were identified by in vivo biopanning, that is, by injecting the phage into the circulation and selecting those phages that specifically bound to the liver. One theoretical advantage of this technique is that it identifies genes whose expression is not merely correlated with the process of metastasis but rather those whose function is directly integral to the mechanism itself.

As more novel and precise methods for metastasis gene discovery are developed and consequently, more specific metastatic gene products are identified, so also, ideally, will the therapeutic targeting of the metastatic process become more focused and efficacious.

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