Researchers have uncovered the mechanism by which a protein facilitates the spread of breast cancer cells from the primary tumor into healthy tissue. The discovery not only improves our understanding of the metastatic process but is the first step to developing treatments that target this mechanism.
Cancer’s ability to spread or metastasize from the primary tumor to invade healthy tissue is one of its most lethal features. In almost 30% of women with early-stage breast cancer, the cancer metastasizes, most commonly to the bones.
Now, researchers from Pennsylvania State University (Penn State) have discovered that a protein called dynein is indispensable to the process of metastasis in breast cancer, providing a new therapeutic target that has the potential to stop cancer in its tracks.
“This discovery marks a paradigm shift in many ways,” said Erdem Tabdanov, a co-corresponding author 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.”
Motor proteins such as dynein are fueled by chemical energy and are essential for the movement, division and spatial organization of eukaryotic cells, or cells that possess a nucleus. To investigate the role of dynein, the researchers examined how live breast cancer cells migrated using two human models.
The first, a two-dimensional network of collagen fibers, showed how cancer cells moved through an extracellular matrix surrounding tumors and how dynein was key to that movement. The second was designed to mimic soft tissue using a network of microscopic hydrogel particles, microgels, linked together in 3D tumor-like shapes. As with the first model, the researchers found dynein was necessary for the movement of cancer cells.
“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,” said Amir Sheikhi, another corresponding author. “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.”
The researchers say that, following the surgical removal of a tumor, paralyzing any remaining cancer cells might be an effective and less toxic alternative to chemotherapy.
“The trick with chemotherapy is to kill the cancer cells slightly faster than the rest of the body – it’s a race against time,” said Tabdanov. “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 healthier.”
Any potential treatment targeting dynein is still far off, but the study is an important first step in stopping the spread of breast cancer.
The study was published in the journal Advanced Science.
Source: Penn State