Ellen Beswick, PhD, studies a protein that could be key in attacking cancers of the colon and rectum, and possibly other cancers, too. Beswick studies granulocyte-colony stimulating factor, or G-CSF, and its receptor. It’s a signaling protein that helps bone marrow stem cells to mature into different types of blood cells and flow into the bloodstream. But Beswick has learned that it may do more. She’ll use a new $ 1.7 million five-year federal grant to study how blocking G-CSF in tumors keeps them from growing and helps immune cells to attack them.
Beswick’s research has shown that colon and stomach tumors have more G-CSF and G-CSF receptor than normal tissues. She has also shown that, at least in mice, blocking G-CSF made these tumors shrink and brought more and different kinds of immune cells into them. She’s using the new grant to study how G-CSF affects immune cells and which types it affects. She’ll also study how G-CSF keeps tumor cells from multiplying and spreading. And she’ll confirm her findings in human tumor tissues. “Most new treatments either focus on stopping tumor growth or on immunotherapy to turn on good immune responses,” Beswick says. “I think this could do both.”
Cancers of the colon and rectum remain one of the most common types of cancers worldwide. In New Mexico alone, the American Cancer Society estimates that 760 people will receive diagnoses of these cancers and 350 will die from it. Beswick’s research could lead to new approaches against these cancers.
“The goals in the new project are to understand the mechanisms of how G-CSF is regulating immune responses in the tumor microenvironment,” says Beswick. “One of the big problems in the tumor microenvironment is that the signals are telling the immune cells not to have positive activity.” She explains further that tumor cells send signals to immune cells to shut them down or worse, to help the tumor grow.
Beswick was the first to show that blocking G-CSF drew three different kinds of immune cells into the tumor: macrophages, T-cells and natural killer cells. In mice, blocking G-CSF almost completely shrunk their tumors. “No one had done any of that work before,” says Beswick.
The new grant will help Beswick to study the proteins that G-CSF affects and learn more about the G-CSF receptor. She’s also interested in other tumor types that have high levels of G-CSF. “It’s in a lot of human tissues,” says Beswick. “It seems to be linked with tumors that had lymph node metastases.”
Treatment for people is still some time off. “Treatments will have side effects, or some good properties and some bad properties,” Beswick says. So, she’ll need the help of a team to design a new drug for human use. The drug must then go through clinical trials to get Food and Drug Administration approval. But this scientific work could lead to new and better approaches against colorectal cancers. Says Beswick, “It’s important to me to have a translational aspect, which means experiments that would be applicable to humans, and work towards that goal.”
Ellen Beswick, PhD, is an Associate Professor in the Department of Molecular Genetics & Microbiology at The University of New Mexico School of Medicine. She is a full member of the Translational Cancer Biology and Signaling research program at the UNM Comprehensive Cancer Center. Her research program examines several novel inflammatory pathways in gastrointestinal cancers that link inflammation and tumor development and progression. She studies the interplay between the gastrointestinal tumor microenvironment and immune cells, which leads to tumor growth. The long term goal of this work is to develop new therapeutics to target these diseases.
The National Cancer Institute of the National Institutes of Health supports the research reported in this publication under Award Number 1R01CA207051-01, Principal Investigator: Ellen J. Beswick, PhD. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
The University of New Mexico Comprehensive Cancer Center is the Official Cancer Center of New Mexico and the only National Cancer Institute-designated Cancer Center in a 500-mile radius. One of the premier cancer centers nationwide, the UNM CCC has more than 125 board-certified oncology physicians, forming New Mexico’s largest cancer care team. It treats about 60 percent of adults and virtually all the children in New Mexico diagnosed with cancer — more than 10,000 people— from every county in the state in more than 135,000 clinic visits each year. Through its partnership with the New Mexico Cancer Care Alliance, an “exemplary national model for cancer health care delivery,” the UNM CCC offers access to more than 175 clinical trials to New Mexicans in every part of the state. Annual research funding of almost $60 million supports the UNM CCC’s 130 cancer scientists. Working with partners at Los Alamos and Sandia National Laboratories, Lovelace Respiratory Research Institute, and New Mexico State University, they have developed new diagnostics and drugs for leukemia, breast cancer, ovarian cancer, prostate cancer, liver and pancreatic cancer, brain cancer, and melanoma. Learn more at cancer.unm.edu.
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