Cancer Treatment Gets Huge Nudge From Blind Mole Rats?

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Blind mole rats may hold the key to curing cancer. Image by Vivan755

The adage ‘Nature is the best teacher’ rings very true for the study on blind mole rats, published by Dr. Shams group. The study focuses on blind mole rats (Spalax) that live in the wild, in solitude, are non-inbred and most importantly, cancer resistant. Additionally, these blind mole rats show the fascinating characteristics of delayed ageing; no age-related decrease in life span, and high fertility until death.

These subterranean rodents never suffer from spontaneous tumors, and nor do their cousins, the naked mole rat (Heterocephalus glaber). Now that’s impressive, given that the hundred other animals used either for laboratory research or in the wild don’t possess immunity to this disease.

Stress Response: How Do Blind  Mole Rats Cope?

Of course, the immediate question then is: what makes these creatures so special? The secret is the blind mole rat’s body has adapted extremely well to their stressful lifestyle. The co-author of this study, Eviator Nevo explains it thus in Nature, “These animals are subject to terrific stresses underground: darkness, scarcity of food, immense number of pathogens and low oxygen levels.”

One prominent culprit that underlies various diseases like cancer is hypoxia, or low oxygen levels and oxidative stress. Hypoxia can result in a failure to maintain normal cellular metabolism. The special ability of the blind mole rats to combat and cope with hypoxia is due to their high muscular mass, high density of blood vessels, and efficient oxygen delivery.

In addition, these rodents have substituted sequences in their genes or possess splice variants, to enable them to cope with these stressors. A glimpse of the blind mole rat’s mRNA transcripts genome-wide reveals an enrichment of genes that are involved in cancer resistance; apoptosis (cell death) and hypoxia-tolerance.

Spalax also have higher levels and modified versions of reactive oxygen species (ROS) processing enzymes like Nrf2 and heme-oxygenase-1 (HO-1).

Cancer-free Mole Rats: What’s the Secret?

In a previous study led by Professor Vera Gorbunova and Assistant Professor Andrei Seluanov, the researchers showed that these rodents have a neat way of killing pre-cancerous and cancerous cells by secreting a protein: interferon-beta.

In the latest study published last week, Dr. Sham and colleagues exposed these Spalax rodents to two chemical inducing carcinogens, and very strikingly, only 1 out of 12 animals developed tumors. This is in contrast to mice, where all 12 mice developed cancer.

Tumor growth requires help from growth factors present in the surrounding stroma. Normal stromal cells contain a small number of fibroblasts, which are an integral part of connective tissue and are required for normal development and wound healing.

In tumors and during wound healing, the stromal fibroblasts become activated, and secrete more growth factors and cytokines, and multiply rapidly.

The speciality of Spalax’s fibroblasts was evident when the authors demonstrated that Spalax’s fibroblasts could inhibit growth of lung and breast cancer cells. This interaction is specific, because the removal of Spalax’s fibroblasts leads to the recurrence of tumor cell.

It would be very informative to figure out the specific factors present in Spalax’s cells that render them powerful against cancer. And of course, that is the next step in Dr. Sham’s research.

Blind Mole Rats: Animal Models for Cancer

As Prof. Robert Weinberg at MIT put it, in BMC Biology, “The classical mice model for cancer research has little predictive value and a negligible relation to that of human. Far more than anything else, the lack of good animal models has become the rate-limiting step in human cancer research.

The remarkable workings of Spalax rodent can be used to address some of the most challenging questions in biology: How to defy ageing, how to make the most of extreme climates, how to live in low oxygen environments, how to maintain high fertility till end of life, how to live long lives and most importantly, how to live cancer-free.

References

Manov I., et allPronounced cancer resistance in a subterranean rodent, the blind mole-rat, Spalaxin  vivo and in vitro evidence. (2013). BMC. Accessed September 5, 2013.

Cormier Z. Blind mole rats may hold key to cancer. (2012). Nature. Accessed September 5, 2013.

Gorbunova V., et all. Cancer resistance in the blind mole rat is mediated by concerted necrotic cell death mechanism. (2012). PNAS. Accessed September 5, 2013.

Kim E.B., et allGenome sequencing reveals insights into physiology and longevity of the naked mole rat. (2011). Nature: International Weekly Journal of Science. Accessed September 5, 2013.

Kalluri R and Zeisberg M. Fibroblasts in cancer. (2006). Nature Reviews Cancer. Accessed September 5, 2013.

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