Thursday, June 20, 2013

Hyaluronan - Cancer-Proof "Goo" From Naked Mole Rats May Lead To New Treatments

Cancer-Proof "Goo" From Naked Mole Rats May Lead To New Treatments 

Article Date: 20 Jun 2013 - 3:00 PDT 

Despite its long lifespan, the naked mole rat has never been known to get cancer. Now scientists in the US have discovered this is thanks to a simple chemical in the "goo" of the rodent's skin, which they suggest could lead to new anti-cancer treatments in humans. 

The team, led by Andrei Seluanov and Vera Gorbunova from the University of Rochester, New York, report their findings in the 19 June online issue of Nature. 

High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat 
Xiao Tian, Jorge Azpurua, Christopher Hine, Amita Vaidya, Max Myakishev-Rempel, Julia Ablaeva, Zhiyong Mao, Eviatar Nevo, Vera Gorbunova & Andrei Seluanov 
AffiliationsContributionsCorresponding authors 
Nature (2013) doi:10.1038/nature12234 
Received 15 June 2012 Accepted 30 April 2013 Published online 19 June 2013 

The naked mole rat (Heterocephalus glaber) displays exceptional longevity, with a maximum lifespan exceeding 30?years1, 2, 3. This is the longest reported lifespan for a rodent species and is especially striking considering the small body mass of the naked mole rat. In comparison, a similarly sized house mouse has a maximum lifespan of 4?years4, 5. In addition to their longevity, naked mole rats show an unusual resistance to cancer. Multi-year observations of large naked mole-rat colonies did not detect a single incidence of cancer2, 6. Here we identify a mechanism responsible for the naked mole rat’s cancer resistance. We found that naked mole-rat fibroblasts secrete extremely high-molecular-mass hyaluronan (HA), which is over five times larger than human or mouse HA. This high-molecular-mass HA accumulates abundantly in naked mole-rat tissues owing to the decreased activity of HA-degrading enzymes and a unique sequence of hyaluronan synthase 2 (HAS2). Furthermore, the naked mole-rat cells are more sensitive to HA signalling, as they have a higher affinity to HA compared with mouse or human cells. Perturbation of the signalling pathways sufficient for malignant transformation of mouse fibroblasts fails to transform naked mole-rat cells. However, once high-molecular-mass HA is removed by either knocking down HAS2 or overexpressing the HA-degrading enzyme, HYAL2, naked mole-rat cells become susceptible to malignant transformation and readily form tumours in mice. We speculate that naked mole rats have evolved a higher concentration of HA in the skin to provide skin elasticity needed for life in underground tunnels. This trait may have then been co-opted to provide cancer resistance and longevity to this species. 

From the Head of a Rooster To a Smiling Face Near You 

Published: December 23, 2003 

It starts with a chicken, not an egg. 

The red combs of roosters and hens turn out to be some of the best sources for the sugar molecule hyaluronan, a compound that some doctors are calling the next big thing after Botox. 

It is already used to protect the eye during surgery, reduce inflammation in arthritic knees and prevent postsurgery scar tissue. Most recently, hyaluronan has become known as the latest treatment for plumping up facial wrinkles. 

Hyaluronan, formerly known as hyaluronic acid, may have many more applications, researchers and doctors hope, as they search for ways to harness its potential to manipulate cells. 

Hyaluronan was discovered in 1934 by Karl Meyer in an ophthalmology lab at Columbia University. Meyer found the substance in cows' eyes and determined that it helped the eye retain its shape. The substance was very viscous, leading Meyer to suspect that it might have some therapeutic use. 
To extract the product, Pfizer and another major manufacturer, Genzyme, follow essentially the same process. 

Genzyme, of Cambridge, Mass., starts with garden variety chickens from Northeastern farms. The combs are removed after slaughter (the chickens are sold for food), frozen and shipped to the manufacturing plant. Freezing helps destroy bacteria. But when the combs arrive at the plant, they are raised to room temperature and sliced into chips. The chips are dumped in a huge vat where they are washed to remove remaining bacteria, feathers, blood or other contaminants. 

At Genzyme, about 1,300 pounds of combs are processed in a single vat. The vat is drained, and water is pumped in. Hyaluronan is water soluble, so it leaches into the water. 
Scientists used to think hyaluronan had just a physical, structural role. But researchers have found that it influences the way that cells act, said Dr. Bryan Toole, a professor of cell biology and anatomy at the Medical University of South Carolina. 

At a conference in October held by Dr. Balazs and Dr. Hascall at the Cleveland Clinic, 300 researchers presented data on hyaluronan's potential to heal wounds, prevent scarring and deliver slowly released drugs to precise areas. 

Some early studies, including a few by Dr. Toole, have shown that hyaluronan may help cancer cells migrate through the body. Scientists are trying to figure out how to manipulate the molecule to stop that action. Dr. Toole said he was talking to a company about this area of research, but was unable to say more about it yet.