Fox Chase, Temple University Researchers Develop Further Insight Into How Cells Metastasize in Breast Cancer

PHILADELPHIA (September 27, 2022)—In a recently published study, researchers at Fox Chase Cancer Center and Temple University found that only a few so called “leader cells” are necessary for metastasis of breast cancer—the spread of cancer cells from their point of origin to other parts of the body—to occur. The finding underscores the need for more personalized and targeted approaches to fighting cancer.

“In this study we show that cells that are invasive and metastatic can not only metastasize themselves but can form groups with other cells and help them move across vessels and metastasize, even though these other cells are not invasive,” said Bojana Gligorijevic, PhD, the study’s lead author.

Gligorijevic is an associate professor in the Cancer Signaling and Epigenetics research program at Fox Chase, where she also co-directs the Biological Imaging Facility. She is also an associate professor of bioengineering at Temple University College of Engineering and associate professor at the Fels Cancer Institute for Personalized Medicine at the Lewis Katz School of Medicine, Temple University.

In the study, researchers created a mixture of cells composed mainly of those unable to metastasize, known as noninvasive cells, with a few that could metastasize, known as invasive cells. They then placed them into a spheroid, a 3-D cell model that can mimic tissues and micro-tumors.

Researchers used collagen as the matrix to mimic breast tissue. The cell matrix is a large group of proteins and molecules that give the cell its outer structure. They then colored the noninvasive cells green and the invasive cells pink and monitored their behavior for several days.

Their observations revealed that all the pink invasive cells reorganized and traveled to the edge of the spheroid, creating a pink ring in direct contact with the matrix. The green cells, however, continued to randomly move within the circle.

In the next step, Gligorijevic said, the pink cells—referred to as the “leader cells”—started digging through the surrounding matrix, making tunnels to where the green, noninvasive cells eventually followed.

“We refer to this phenomenon as cooperative invasion, where the invasive pink leader cells enable the noninvasive green cells to move and invade through the dense environment,” said Gligorijevic. Similarly, leader cells can help noninvasive cells enter the blood vessels and metastasize in the lung, which is referred to as cooperative metastasis.

“This is very dangerous because it means that only a few metastatic cells are needed to make an entire tumor metastasize. Patients who die of breast cancer, 98% of the time they are patients with metastatic breast cancer.”

She added that this work demonstrates the need for more personalized and targeted approaches to fighting cancer because it shows that it is only necessary to kill the few metastatic cells rather than the entire population of tumor cells.

“Chemotherapy and radiation kill any cell that’s dividing and can kill even healthy cells. Specifically targeting the rare cell population is likely to cause less side effects compared to targeting the whole tumor mass,” said Gligorijevic.

The study, “Invadopodia Enable Cooperative Invasion and Metastasis of Breast Cancer Cells,” was published in Communications Biology.

Fox Chase Cancer Center (Fox Chase), which includes the Institute for Cancer Research and the American Oncologic Hospital and is a part of Temple Health, is one of the leading comprehensive cancer centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase is also one of just 10 members of the Alliance of Dedicated Cancer Centers. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence five consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach. It is the policy of Fox Chase Cancer Center that there shall be no exclusion from, or participation in, and no one denied the benefits of, the delivery of quality medical care on the basis of race, ethnicity, religion, sexual orientation, gender, gender identity/expression, disability, age, ancestry, color, national origin, physical ability, level of education, or source of payment.

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