It’s a pretty unassuming animal. Some people might even say it’s ugly. But while the naked mole rat might not win any beauty contests, scientists are intrigued by some of the qualities common to this subterranean rodent.
The naked mole rat is found in East Africa, primarily in Kenya, Somalia and Ethiopia. Thanks in part to its underground habitat, it has a lot of unique characteristics that set it apart from most other mammals. It’s nearly blind, and like reptiles and amphibians, it’s a thermoconformer. It also lacks the ability to sense pain in its skin, and has low metabolic and respiratory rates. But researchers are drawn to the creature for two unique traits in particular: its remarkable longevity – often as much as 30 years – and the fact that they are extremely resistant to cancer.
It’s that last part that has piqued the interest of researchers like Dr. Barbara Triggs-Raine, a biochemist at the University of Manitoba. She was intrigued by a recent study from scientists at the University of Rochester and the University of Haifa that found the rats’ unusually high concentration of a jelly-like substance called hyaluronan prevents their cells from overcrowding, thereby inhibiting the growth of tumours. When researchers used an enzyme that broke down hyaluronan in the rats, they observed a higher susceptibility to cancer growth.
Triggs-Raine, the recipient of a research grant from the Canadian Cancer Society, is following up on the Rochester/Haifa study, but with a new angle: she’s taking a closer look at that hyaluronan-inhibiting enzyme, known as hyaluronidase 2. What she’s found so far is that most animals maintain a delicate balance between hyaluronan and hyaluronidase 2. Removing the latter in mice, in fact, leads to a range of serious health consequences.
“We know that if you remove this enzyme, hyaluronidase-2, right at the very beginning of development,” she says, “that a significant proportion of the mice don’t actually live to weaning. They die soon after birth…But we also think if you allow hyaluronidase-2 to be there, during development, that everything’s ok because it may not be that critical after the mouse has developed.
“Presumably something similar, we hope, can model the human condition.”
What is hyaluronan?
Hyaluronan is really just a sugar molecule. It’s abundant in just about all animals – as Dr. Triggs-Raine notes, probably the most common sugar that can be found around cells, where it acts as a lubricant. The highest concentrations are in loose connective tissues, our skin, and joints, but it’s also in particularly high concentration in the unbilical cord. It’s hardly surprising, since hyaluronan is believed to play a crucial role in development.
“Hyaluronan absorbs a lot of water and makes it easy for cells to move,” she says. “So when cells are moving during development there’s a lot of it present, and then it decreases as you age.”
It’s already well-known to dermatologists: hyaluronan is a popular component of skin-care products and is used in some medical procedures. “It’s used to space-fill. It’s a great hydrator. It’s not only present naturally in people, but it’s also given to people to try and modify skin wrinkles, or if they just need to put a little bit of material in to let cells grow around.”
A promising development for cancer research
The theory is that the naked mole rats’ unusually high abundance of hyaluronan in their bodies serves to protect them against developing cancer. And so the hope is that this discovery might eventually lead to therapies that utilize hyaluronan in order to either reduce susceptibility to certain cancers, or reduce their ability to spread.
Dr. Triggs-Raine acknowledges that the research is still in its early stages, with any possible treatment likely residing over a decade into the future. But she is quick to suggest where such therapies might be most likely to be used. Given that hyaluronan is most abundant in the skin – that’s where 50 per cent of it is found – she sees a good possibility of new skin cancer therapies eventually developing from this line of research.
But she’s quick to reiterate that hyaluronan resides in just about every other tissue in the body as well: the heart and muscles, for instance. And so there’s the potential for a broad spectrum of eventual applications.
That, she says, is really the best part about this discovery: it potentially offers a range of new possibilities.
“These things that take us in new directions are maybe more likely to have a greater impact, because you’re providing a whole new approach to therapy.”