After researchers eliminated CAFs in mice, tumors in the lungs, image b, and in the bones, image d, metastesized within 10 days. Photo by Biju Parekkadan/Massachusetts General Hospital
BALTIMORE, Feb. 19 (UPI) -- Researchers thought killing cells that help cancerous tumors grow would slow or halt their progression but found instead their elimination increased the chance for cancer metastasis, according to a recent study.
When trying to limit the growth the breast cancer tumors in mice, researchers at Harvard Medical School found that getting rid of cancer-associated fibroblasts, or CAFs, increased metastasis of cancer to the lungs and bones in the rodents.
CAFs are thought to be native fibroblast cells, responsible for the structural framework of animal tissues, hijacked by cancer cells to sustain tumor growth.
Most cancer deaths are caused by metastasis to other organs, rather than from the primary tumor, making results of the recent study important at least for future research.
"The simplistic thinking about CAFs is that we should probably try to destroy them," Dr. Biju Parekkadan, an assistant professor of surgery and bioengineering at Massachusetts General Hospital, said in a press release. "There is evidence to support this idea, and until recently, I would have been in that camp as well. But now when looking at the selective removal of CAFs over time using this engineered approach, these results may be a signal that we should more fully investigate the dynamics of the tumor microenvironment and the timing of intervention in cancer treatment."
For the study, published in Scientific Reports, researchers implanted breast cancer cells in mice with CAFs they had altered to die when exposed to a compound not toxic to surrounding cells.
The researchers killed the CAFs at two stages of tumor growth after implantation, on the third or fourth day and on the 10th or 11th day. When CAFs were killed earlier, there was no major difference in tumor growth but there was an increase in tumor-associated macrophages, which are associated with metastasis at the tumor's growth stages.
CAFs killed after 10 or 11 days not only increased macrophages, but the researchers reported cancer became more likely to spread to lungs and bones of the rodents.
Calling the results of waiting longer to kill CAFs "surprising," the researchers said future work should focus on timing of killing CAFs, but more importantly on whether there is a scientific basis for targeting the cells at all.
"This work underscores two important things in solving the puzzle that is cancer," said Dr. Rosemarie Hunziker, program director for Tissue Engineering at the National Institute of Biomedical Imaging and Bioengineering. "First, we are dealing with a complex disease with so many dimensions that we are really only just beginning to describe it. Second, this approach shows the power of cell engineering -- manipulating a key cell in the cancer environment has led to a significant new understanding of how cancer grows and how it might be controlled in the future."