Identifying Metastatic Breast Cancer

A new microarray method helps researchers identify markers of non-metastatic and metastatic breast cancer cells, according to a new study that may lead to better prognostics and therapeutics for breast cancer.

Researchers used microarrays to analyze variations in gene activity between cancer cell lines with differing capability to spread to distant organs but derived from the same human breast cancer. This eliminates the problem of irrelevant genetic variability among tumors derived from different patients.

In the study, three cell lines were used that were weakly, moderately, or highly metastatic when injected into mice with compromised immune systems. The injected cells were labeled with green fluorescent protein (GFP) so dissemination of the cancer cells could be accurately tracked by their green glow. Each of the three cell lines was injected into the mammary pads of mice, and metastasis was monitored by examining migration of cells to the lymph nodes and lungs.

The weakly metastatic cells rarely moved to other sites, while the moderately and highly metastatic cells migrated at increasing frequencies. The resulting primary and secondary tumors were then harvested for gene expression analysis by a microarray. Using a gene chip of 22,000 genes, the researchers determined which genes were turned "on” and "off” in primary versus metastatic tumors. They found few differences between the genes expressed in primary and secondary tumors originating from the same injected cell line. However, comparisons between non-metastatic and highly metastatic tumors identified several genes with altered expression patterns. This was confirmed by analyzing RNA and protein levels from the tumors in vivo and the original cell lines in culture.

As envisioned by Dr. David Tarin, "further work using this strategy will identify collections of marker genes that predict the future behavior of a given human cancer from samples taken from the patient. The aim is to minimize over-treatment of those who do not need it and avoid under-treatment of those patients who do.” The study was performed in the laboratory of Dr. Tarin, of the University of California, San Diego (CA, USA), and the findings were published in the May 2005 issue of The American Journal of Pathology.




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