“Our work shows that the ability of a tumour to form metastases depends on the combined action of multiple genes – and a different set of genes is required for each organ the tumour spreads to,” said Joan Massagué, PhD, Chairman, Cancer Biology and Genetics Program, at MSKCC, who led the study. “Based on these insights, we can now seek genes for metastasis by other tumours and to other organs,” Massagué added.
The latest work shows that the genes that prompt breast tumours to spread to the lungs are almost entirely different from the earlier set, with only six genes in common. This finding is surprising as it had been previously assumed that genes that dictate metastases to specific organs did not exist.
To uncover genes involved in breast cancer metastasis, Dr. Massagué’s group used a cell line from a breast cancer patient treated for aggressive tumours that had spread to many other organs. From this line they identified cancer cells that showed a propensity for migrating to the lungs but not the bone when transplanted into mice.
Using a microarray the researchers were able to analyse the cells to see how their genetic activity differed from that of breast cancer cells that did not show a proclivity for lung metastases in the rodents. Some genes function more vigorously than usual while the activity of others was suppressed.
The gene “thumbprint” was then verified in a group of 82 early stage breast tumours removed from patients at MSKCC. More than half (55 percent) of patients whose primary tumours showed the genetic thumbprint went on to develop lung metastases, compared with only ten percent of those whose primary tumours did not carry the gene set.
“Metastasis, particularly to visceral organs such as the lung, accounts for the majority of breast cancer related mortality,” said Andy J. Minn, MD, PhD, a radiation oncologist at MSKCC. The new research “may provide genetic markers to aid oncologists in clinical management, offer potential therapeutic targets to develop drugs against metastasis, and give basic researchers a paradigm to understand how metastatic ability is acquired,” Minn said.
MEDICA.de; Source: Memorial Sloan-Kettering Cancer Center