05:16pm Tuesday 21 November 2017

Low Oxygen Recruits Inflammatory Cells to Tumors, Stimulating Growth, Penn Researchers Find

“We know that hypoxia affects many aspects of tumor progression, but this is another novel way that it clearly does, by recruiting inflammatory cells,” says Celeste Simon, PhD, professor of Cell and Developmental Biology, who presented the results in a symposium on Wednesday, April 21st, at the American Association of Cancer Research annual meeting.

“It is clear that macrophages accumulate in hypoxic, or low oxygen, regions of patient tumor samples,” continues Simon, who is also a Howard Hughes Medical Institute investigator. “And it has been inferred that the factors that respond to low oxygen would actually have a positive effect on tumor growth.”

The team deleted a hypoxia inducible gene from macrophage cells in mice and then analyzed what happened in colon and liver cancer models. The macrophages that lacked the hypoxia inducible factor did not accumulate in tumors in both cancer models. As a result, the tumors in the genetically deficient mice were smaller, had fewer blood vessels, and did not progress to a higher stage of disease.

Teasing apart this mechanism, the researchers found that the hypoxic tumor cells secrete chemicals that normally bind to receptors on the surface of macrophages. Without the hypoxia inducible gene, the macrophages expressed less of the receptor and so did not respond to the tumor growth signals.

With that information in hand, Simon surmises the team has uncovered a possible new drug target for cancer therapy. “If you can come up with a well tolerated anti-inflammatory drug, that could work out very well,” she said.

 

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Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System, which together form a $3.6 billion enterprise. 

Penn’s School of Medicine is currently ranked #2 in U.S. News & World Report’s survey of research-oriented medical schools, and is consistently among the nation’s top recipients of funding from the National Institutes of Health, with $367.2 million awarded in the 2008 fiscal year. 

Penn Medicine’s patient care facilities include:

Additional patient care facilities and services include Penn Medicine at Rittenhouse, a Philadelphia campus offering inpatient rehabilitation and outpatient care in many specialties; as well as a primary care provider network; a faculty practice plan; home care and hospice services; and several multispecialty outpatient facilities across the Philadelphia region.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2009, Penn Medicine provided $733.5 million to benefit our community.


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