Like naked mole-rats (Heterocephalus gaber), blind mole-rats (of the genus Spalax) live underground in low-oxygen environments, are long-lived and resistant to cancer. A new study demonstrates just how cancer-resistant Spalax are, and suggests that the adaptations that help these rodents survive in low-oxygen environments also play a role in their longevity and cancer resistance.
The findings are reported in the journal Biomed Central: Biology.
"We've shown that, compared to mice and rats, blind mole-rats are highly resistant to carcinogens," said Mark Band, the director of functional genomics at the University of Illinois Biotechnology Center and a co-author on the study. Band led a previous analysis of gene expression in blind mole-rats living in low-oxygen (hypoxic) environments. He found that genes that respond to hypoxia are known to also play a role in aging and in suppressing or promoting cancer.
"We think that these three phenomena are tied in together: the hypoxia tolerance, the longevity and cancer resistance," Band said. "We think all result from evolutionary adaptations to a stressful environment."
Unlike the naked mole-rat, which lives in colonies in Eastern Africa, the blind mole-rat is a solitary rodent found in the Eastern Mediterranean. Thousands of blind mole-rats have been captured and studied for more than 50 years at Israel's University of Haifa, where the animal work was conducted. The Haifa scientists observed that none of their blind mole-rats had ever developed cancer, even though Spalax can live more than 20 years. Lab mice and rats have a maximum lifespan of about 3.5 years and yet regularly develop spontaneous cancers.
To test the blind mole-rats' cancer resistance, the Haifa team, led by Irena Manov, Aaron Avivi and Imad Shams, exposed the animals to two cancer-causing agents. Only one of the 20 Spalax tested (an animal that was more than 10 years old) developed malignant tumors after exposure to one of the carcinogens. In contrast, all of the 12 mice and six rats exposed to either agent developed cancerous tumors.
The team next turned its attention to fibroblasts, cells that generate extracellular factors that support and buffer other cells. Previous studies of naked mole-rat cells have found that fibroblasts and their secretions have anti-cancer activity. Similarly, the researchers at Haifa found that Spalax fibroblasts were efficient killers of two types of breast cancer cells and two types of lung cancer cells. Diluted and filtered liquid medium drawn from the fibroblast cell culture also killed breast and lung cancer cells. Mouse fibroblasts, however, had no effect on the cancer cells.