Breast Cancer Metastasis Discovery May Offer New Avenues for Treatment

A new study has revealed some of the mechanics underlying how breast cancer cells invade healthy tissues. The research, which may offer new drug targets against the spread of cancer cells (metastasis), is published in Advanced Science.

Metastasis: A key feature of cancer

The ability of cancer cells to spread and migrate around the body is one of the key hallmarks of cancer. Once a cancer has metastasized, treatment options are typically very slim.

Researchers, led by investigators from Penn State, have discovered some of the mechanics cancer cells use to spread and invade healthy tissues.

Using soft tissue models, they found that a motor protein called dynein plays a leading role in metastasis and could potentially represent a promising new treatment target.

“This discovery marks a paradigm shift in many ways,” said Dr. Erdem Tabdanov, assistant professor of pharmacology at Penn State and one of the co-senior authors of the study. “Until now, dynein has never been caught in the business of providing the mechanical force for cancer cell motility, which is their ability to move themselves. Now we can see that if you target dynein, you could effectively stop motility of those cells and, therefore, stop metastatic dissemination.”

Dynein “indispensable” in laboratory models

The study is the result of a collaboration between Penn State’s Department of Chemical Engineering and College of Medicine, which eventually grew to receive input from other institutions such as the University of Rochester, Georgia Institute of Technology, Emory University and the US Food and Drug Administration (FDA).

The researchers used live microscopy to observe the movement and migration of breast cancer cells, monitoring how they migrated through two-dimensional and three-dimensional systems modeled after the human body.

First, they used a two-dimensional network of collagen fibers to mimic the extracellular matrix that surrounds tumors, observing that dynein was essential for the cancer cells’ movement.

Next, a three-dimensional model was used, developed by Dr. Amir Sheikhi, an assistant professor of chemical and biomedical engineering at Penn State. This second system uses a network of microscopic hydrogel particles linked together to create tumor-like shapes and mimic soft tissue. This revealed that dynein was “indispensable” in cancer cell spread.

“Using these three-dimensional models that partially mimic a tumor, we discovered that if we block the dynein, the cancer cells cannot effectively move and infiltrate solid tissues,” Sheikhi explained.

“In both models, we found that dynein is extremely important for cell locomotion, which suggests a whole new method for cancer management. Instead of killing the cancer cells with radiation or chemotherapy, we are showing how to paralyze them. This is great news because you don't really have to kill the cells, which is a harsh approach that targets both cancerous and healthy cells. Instead, you just have to stop the cancer cells from moving,” he added.

“Paralyzing” cancer cells

Targeting mechanisms relating to dynein function and inducing “paralysis” of cancer cells could represent a possible treatment strategy, Tabdanov noted, explaining that it could be used after surgical removal of tumors to prevent the spread of any remaining cells without damaging healthy tissue. However, as new treatments require extensive studies in animals and humans, further research will be required before this is a reality.

“The trick with chemotherapy is to kill the cancer cells slightly faster than the rest of the body – it’s a race against time,” Tabdanov said. “Chemotherapy causes a lot of damage to the body’s normal, healthy tissues while it is busy killing the cancer. If we instead contained the cancer, stopped it in its tracks, we could keep the healthy parts of the body healthy.”

“We are very excited about this collaboration with the Penn State College of Medicine, and our labs are working closely on other projects,” said Sheikhi. “I think these platforms could one day enable personalized medicine and personalized treatment for cancer and, hopefully, many other diseases.”

Reference: Tagay Y, Kheirabadi S, Ataie Z, et al. Dynein-powered cell locomotion guides metastasis of breast cancer. Adv Sci. 2023. 2302229. doi: 10.1002/advs.202302229

This article is a rework of a press release issued by Penn State. Material has been edited for length and content.