A research team has found that the genes that some breast cancer cells express are more likely to help them prosper in bone tissue.
When cells from a primary tumour circulate through the body and begin growing in a new organ, a metastatic tumour is formed. Such metastases are often harder to treat than primary tumours; the vast majority of people who die of cancer have not only a primary tumour but also metastatic disease.
HHMI investigator Joan Massague of Memorial Sloan-Kettering Cancer Center and his colleagues took another look at breast tumours that had SRS turned on. They tested whether there were any other genes, outside the known SRS pathway, that were always turned up on down in the same cells.
They homed in on two—CXCL12 and IGF1—that were not only found to be more highly expressed in tumours with SRS, but were also independently predictive of which tumours would migrate to the bone. Tumours with both genes turned up were more likely to lead to bone metastases.
But in the breast tumours with high levels of CXCL12 and IGF1, the researchers found, the genes weren’t originating from cancer cells. Tumours consist of not only cancerous cells, but also other supporting cells that are integrated into the tumours’ structure.
The gene signature, it turned out, was coming from noncancerous mesenchymal cells integrating into the breast tumour. And not only that, but CXCL12 and IGF1 were also known to be expressed by bone cells. The genes, in both cases, encoded signalling molecules called cytokines.
Biochemical experiments revealed that when the mesenchymal cells supporting a tumor have CXCL12 and IGF1 turned on, and produce lots of cytokines, nearby cancer cells are selected for SRS activation.
The SRS gene signature, while it doesn’t significantly change primary breast tumour growth, makes cancerous cells slightly more sensitive to the cytokines produced by the mesenchymal cells. Then, because they are more sensitive to these cytokines, if the cells end up in bone tissue that expresses higher levels of the same cytokines, they will grow more aggressively.
The new findings have been published in the journal Cell. (ANI)