Tumours in mice had reduced growth after brown fat, which burns sugars and other fuel that tumours need to grow, was implanted nearby. Researchers used CRISPR gene editing to convert white fat, which can be collected via liposuction, into brown fat
Implanting brown fat around cancerous tumours could halve their size as the fat burns the fuel tumours need to grow. Although only tested in mice and human tissue to date, white fat could one day be extracted from people via liposuction and genetically engineered using the CRISPR technique to turn it into brown fat that then starves tumours of nutrients such as sugar.
Brown fat, mainly found in newborn humans and hibernating mammals, burns other fats and sugars to create heat. Adult humans, however, mostly have white fat, which stores these fuels for energy.
To assess whether brown fat could take these nutrients away from tumours, Nadav Ahituv at the University of California, San Francisco, and his colleagues used the CRISPR technique to increase the expression of a gene called UCP1 in human white fat, causing it to convert to engineered brown fat.
They then injected human breast, prostate or pancreatic cancer cells into mice to form tumours, before implanting either white fat or the engineered brown fat next to these tumours.
The tumours surrounded by brown fat grew to less than half the size of those surrounded by white fat.
In another part of the experiment, the researchers implanted engineered brown fat next to the breasts or pancreases of mice that had been genetically engineered to develop cancer in these tissues. Their tumours were up to two-thirds smaller than those of other mice, who were also genetically engineered to develop these cancers, who received white fat.
None of the mice experienced any observable side effects.
Read more: Cold exposure stops tumour growth in mice by hijacking glucose stores
Finally, the researchers collected white fat from the breast tissue of five women who had undergone breast cancer surgery. They then genetically converted it to brown fat and incubated it in a dish with miniature tumours grown from the same women’s cancer cells.
This incubation reduced the size of the breast tumours by up to two-thirds, compared with when they were incubated with white fat.
Andrew Hoy at the University of Sydney, Australia, says the study builds on recent research that shows that exposing mice with cancer to cold temperatures suppresses their tumour growth by activating brown fat.
Jeff Holst at the University of New South Wales, Australia, notes that the brown fat didn’t eliminate the tumours altogether, which can be achieved with some existing treatments, including immunotherapies, for certain cancer types.
Ahituv says his team is experimenting with increasing the expression of other genes in brown fat, in addition to UCP1, to potentially boost the treatment’s efficacy.
We also need to rigorously test the safety of the engineered brown fat and determine the quantity that must be implanted into animals to have an effect, before testing it in people, he says. One potential risk is that implanting too much of it could result in excessive weight loss as it burns fats and sugars, says Ahituv.
If the approach is shown to be safe and effective in people, it would be relatively simple to implement in the clinic, he says. “There are already approved procedures for removing fat with liposuction and then putting it somewhere else. We would just need to engineer the fat in between these procedures,” he says.
Reference: bioRxivDOI: doi.org/10.1101/2023.03.28.534564