by Bob Owen
Cancer immunity of strange underground rat revealed
[Via Ars Technica]
Researchers have discovered how one of the world’s oddest mammals developed resistance to cancer, and there is hope that their work could help fight the disease in humans.
Naked mole rats live underground, where environmental conditions are harsh but predators are few. They can live for more than 30 years, almost seven years longer than their close cousin the house mouse—which is particularly susceptible to cancer. They breathe slowly due to the limited supply of oxygen, survive on very little food, have poor sight, and are largely indifferent to pain.
Naked mole rats are also the only mammals that do not regulate their body temperature. Because they live in colonies where the queen rat does the job of producing progeny and only a few males father the litters, their sperms become lazy.
I had heard of hyaluronan as an important component of cartilage. But here we see possible evidence of a much more important role.
Could this molecule stop cancer cells from growing? Some previous work suggests that higher hyaluronan levels correlate with more tumors.
Hard to know just what is going on here, as higher hyaluronan levels have been correlated with tumor growth. But maybe this is an effect of the body trying, and failing, to control cell growth. It is an effect not a cause.
But several of the enzymes that degrade hyaluronan also suppress tumors.
The mole rat hyaluronan has much greater mass than human and that may make the difference. According to the paper, the mole rats molecules are quite unusual.
The authors mentioned this:
While culturing multiple lines of naked mole-rat fibroblasts we noticed that the culture media became very viscous after a few days.
This viscosity is not seen with human, rat or guinea pig cells grown in culture.
It turns out that naked mole rats show much greater inhibition of cell density. Most cells stop growing when they contact other cells – contact inhibition. Cancer cells lose this inhibition.
The cells of naked mole rats stop growing at much lower densities than mouse cells. Unless they do not make hyaluronan. Then they display the same cell densities as mice do.
It turns out that one of the major enzymes that produces high molecular weight hyaluronan in naked mole rats has 2 amino acid changes not seen in any other mamal. These two amino acids are 100% conserved in every other mammal. Except naked mole rats.
And when this unusual enzyme is produced human cells, the same high molecular hyaluronan seen in naked mole rats is now seen.
So it looks like the enzyme that produces hyaluronan in naked mole rats may be the guilty party.
It will be very interesting to see how this plays out.
Of course, naked mole rats live for 30 years instead of 3, as normal rats do. They have no hair and loose wrinkly skin. And lazy sperm. And teeth that grow outside their mouth.
Could a cure for cancer come at the cost of living for 700 years with no hair , nasty dental problems and little chance to have offspring?