Cancer Resistance in Blind Mole Rats May Hold Key to Prevention in Humans
November 19, 2012
The blind mole rat may be unsightly, but this subterranean rodent has an extraordinary characteristic – it seems to be impervious to cancer.
Biologists at the University of Rochester recently uncovered why, and the finding may lead to better treatments and prevention techniques for human cancer patients.
The research team, led by Professor Vera Gorbunova and Assistant Professor Andrei Seluanov, studied blind mole rat cells to better understand the mechanism behind the rodent’s assumed immunity to cancer. They determined that abnormal, precancerous cells release a signal that triggers a massive self-destruct reaction, an antitumor response that the researchers dubbed “concerted cell death.”
Recreating this process in human cells could potentially stop cancer growth dead in its tracks.
Rats That Keep Cancer at Bay
In the study, published earlier this month in the Proceedings of the National Academy of Sciences (PNAS), Gorbunova and colleagues investigated the anticancer properties of two species of blind mole rat: Spalax judaei and Spalax golani. These and several other subfamilies of burrowing rodents are native to the Eastern Mediterranean region, with habitats spanning from north Africa to south Turkey.
The blind mole rat’s harsh underground environment has led to remarkable adaptations. These changes have piqued the interest of biologists and cancer researchers alike.
“These animals are subject to terrific stresses underground: darkness, scarcity of food, immense numbers of pathogens and low oxygen levels. So they have evolved a range of mechanisms to cope with these difficulties,” said Eviatar Nevo, a study co-author who has researched the blind mole rat since 1961. “I truly believe work with these animals will bring a dramatic revolution in medicine.”
Compared to other rodents, blind mole rats have a higher density of blood vessels in muscle tissues, an increased lung capacity and a higher red blood cell count. These are all vital adjustments that allow them to thrive in their oxygen-poor burrows. Living in excess of two decades, the blind mole rat is also among the most long-lived of all rodents.
But more importantly, researchers have not once observed cancer in a blind mole rat.
A Unique Antitumor Mechanism
Gorbunova is by no means a novice to research on cancer-resistant rodents. Three years ago, she and Seluanov explained a similar antitumor mechanism in the naked mole rat, the blind mole rat’s seemingly cancer-proof cousin.
PNAS awarded them a prize for the finding, naming their study the most important biomedical research paper of 2009.
As with the blind mole rat, scientists have yet to find evidence of cancer in any naked mole rat. In fact, these two rodents are the only mammals never known to develop the disease. But Gorbunova did not anticipate that the blind mole rat evolved a completely unique antitumor mechanism.
“We thought the blind-mole-rat cells would use the same mechanism as those of naked mole rats,” said Gorbunova, “so the fact that they do not was a big surprise.”
In the 2009 study, Gorbunova discovered that naked mole rat cells behave rather unusually in the lab. When most animal cells are grown on a culture dish, they will continue to divide until a single layer of cells coats the bottom of the container. At this point healthy cells sense the overcrowding and stop dividing, but cancerous ones continue to grow.
Interestingly, the naked mole rat evolved an additional safety net that halts cell division much earlier than the standard process observed in mice and humans. Gorbunova found that a hypersensitivity to overcrowding explained cancer resistance in the naked mole rat.
But instead of using this added mechanism to prevent cancer, cells of the blind mole rat were found to commit mass suicide before they could sense overcrowding and cease to divide.
In the experiment, Gorbunova and Seluanov harvested blind mole rat cells and forced them to divide in a culture dish beyond what occurs in nature. After about 15 to 20 divisions, all of the cells in the dish rapidly died.
“Not only were the cancerous cells killed off, but so were the adjacent cells, which may also be prone to tumorous behavior,” said Seluanov.
Gorbunova explained that the concerted cell death is triggered by the secretion of a signaling protein called interferon-beta. When the cells are dividing in an excessive amount, they collectively release interferon-beta.
“The cells have some way of sensing when they are overproliferating, but we still don’t know precisely how they sense that,” said Gorbunova. “This is what we need to find out next, because it could provide some clue as to how we could activate the same process in human cells.”
Some researchers are skeptical of this finding because scientists have not yet found a way to maintain blind mole rat cell cultures long-term. But Seluanov and Gorbunova remain hopeful, stating that the discovery could lead to new cancer therapies.
“While people don’t use the same cancer-killing mechanism as blind mole rats, we may be able to combat some cancers and prolong life, if we could stimulate the same clean sweep reaction in cancerous human cells,” said Gorbunova.