UNM researcher Ellen Beswick, PhD, studies a molecule that could be key in attacking cancers of the colon and rectum – and possibly other cancers as well.
Granulocyte-colony stimulating factor – or G-CSF – is a signaling protein that normally helps bone marrow stem cells mature into different types of blood cells and flow into the bloodstream. But Beswick has learned that it may play a role in tumor growth.
She’ll use a new five-year $ 1.7 million federal grant to study how blocking G-CSF in tumors keeps them from growing and helps render them vulnerable to the body’s immune cells.
Beswick has found that colon and stomach tumors have more G-CSF and G-CSF receptors than normal tissues. She has also shown in mice that blocking G-CSF made these tumors shrink, allowing more and different kinds of immune cells to attack them.
Beswick is 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 are some of the most common types of cancers worldwide. In New Mexico alone, the American Cancer Society estimates that 760 people will be diagnosed with these cancers and 350 will die from them.
“The goal is to understand the mechanisms of how G-CSF is regulating immune responses in the tumor microenvironment,” Beswick says. “One of the big problems is that the signals are telling the immune cells not to have positive activity.”
Often, she explains, tumor cells send signals to immune cells telling them to shut them down or worse, help the tumor grow.
Beswick was the first to show that blocking G-CSF drew three types of immune cells into the tumor: macrophages, T-cells and natural killer cells. In mice, blocking G-CSF almost completely shrank their tumors. “No one had done any of that work before,” Beswick says.
Beswick is also interested in other tumor types that have high levels of G-CSF. “It’s in a lot of human tissues,” she says. “It seems to be linked with tumors that had lymph node metastases.”
Developing treatments for people is the next step. “Treatments will have side effects, or some good properties and some bad properties,” she says.
She’ll need the help of a team to design a new drug for human use, which then must undergo clinical trials for Food and Drug Administration approval. But this scientific work could lead to new and better approaches against colorectal cancers.
“It’s important to me to have a translational aspect, which means experiments that would be applicable to humans, and work toward that goal,” Beswick says