Mole Rat Stem Cells May Lead to Cancer Breakthrough

Naked mole rats (NMR) were found to have a strong resistance to cancer, and could potentially be used as a unique anti-cancer mechanism that advances future cancer treatments in humans.

According to researchers from Hokkaido University, NMRs can live as long as 30 years, 10 times longer than mice, and appear to almost never have any type of cancer. In the study, researchers used skin fibroblast tissue from adult mole rats.

The cells were reprogrammed to revert to pluripotent stem cells, also known as induced pluripotent stem cells (iPSC). Although iPSCs have the ability to turn into any type of tissue in the body when, and when inserted back into the animal they begin to form tumors called teratomas.

During the study, researchers inserted the mole rat iPSCs into mice with extremely weak immune systems. The results showed that no tumors were formed compared with human iPSCs and mouse iPSCs.

Researchers also found that alternative reading frame (ARF), a tumor suppressor gene, was still active in the mole-rat iPSCs, something that is normally suppressed in human and mouse iPSCs. As for the tumorigenic gene ERAS expressed in mouse embryonic stem cells and iPSCs, they became both dysfunctional and mutated in mole rate iPSCs.

However, once researchers disabled ARF, it forced the expression of the mouse ERAS in mole rat iPSCs, and inserted them into the mice they ended up growing large tumors.

When the ARF gene was suppressed in the mole rat cells during the reprogramming process to iPSCs, cell proliferation stopped with signs of cellular senescence. The opposite happened with mouse cells.

Researchers hypothesize that naked mole rats are protected from developing cancer through the unique process of ARF suppression-induced senescence (ASIS).

“Further research into the detailed mechanisms underlying ASIS in naked mole rats may shed new light on cancer resistance in the mole rats and contribute to the generation of non-tumorigenic human iPSCs, enabling safer cell-based therapeutics,” said researcher Kyoko Miura.