WASHINGTON, DC - The inner regions of tumors have a low-oxygen content and often contain inflammatory cells called macrophages, which researchers suspect promote tumor growth. Now, University of Pennsylvania School of Medicine researchers show that this is the case: Tumor cells in this low-oxygen area actively recruit macrophages and blocking their recruitment reduces tumor growth and aggressiveness in mouse models. The results suggest new targets for cancer drug development.

“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.


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 Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $5.3 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 18 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $373 million awarded in the 2015 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2015, Penn Medicine provided $253.3 million to benefit our community.

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