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Loss of cell adhesion protein drives esophageal and oral cancers in mice
Date:4/12/2011

ormation were derailed because the animals cannot survive throughout embryonic development or immediately after birth without the protein.

To get around that problem, Rustgi and colleagues used a system called Cre-Lox that allows them to remove a particular gene in only a subset of tissues. In this case, the team deleted p120ctn from the oral cavity, esophagus and forestomach. The mutant animals survived through early development and birth, but by 4 to 6 months, most of the mutant animals had developed precancerous lesions and by 9 to 12 months, 70 percent of the mutant animals had full blown tumors. By contrast, none of the control littermates developed cancer.

The investigators noted that as the lesions developed, the tumor cells secreted inflammatory signals that acted like homing signals for immune cells called immature myeloid cells. These cells, in turn, helped to create a microenvironment that supported tumor growth. In fact, when the researchers blocked recruitment of the immune cells, they saw a dramatic reduction in tumor invasion.

Based on these observations, Rustgi thinks that targeting the immature myeloid cells may reverse or slow tumor grown in humans, although more work needs to be done in animal models before the approach is tested in the clinic.

Rustgi says that the mouse model will help test innovative therapies and early detection tests. He says that although he was born and raised in the United States, he was influenced by five years he spent as a child in India, where oral cancer is common due to the proportion of the population that chews betel nuts. "I remember, even as a little kid, I would see people with oral lesions," he says. "I didn't know what they were then, but it has always motivated me at a personal level. Esophageal cancer biology has also been a long-standing interest of mine because it affects so many underserved people in the inner cities in the United States."


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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert

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