New research study has actually discovered that the protein dynein is crucial in breast cancer cell movement, providing a brand-new target for treatments that might “paralyze” cancer cells, potentially using a non-destructive alternative to chemotherapy. Though medical applications are still forthcoming, this advancement uses promising implications for the future of tailored cancer treatment.
The most lethal element of any cancer is metastasis, which is the spread of cancer cells throughout the body. Groundbreaking research led by Penn State has uncovered for the first time the systems that might allow breast cancer cells to attack healthy tissues. This critical discovery exposes that a motor protein called dynein is important in propelling cancer cell motion in models of soft tissue, presenting unique clinical targets for preventing metastasis and potentially transforming cancer treatment.
” This discovery marks a paradigm shift in many methods,” stated Erdem Tabdanov, assistant professor of pharmacology at Penn State and a lead co-corresponding author on the study, just recently published in the journal Advanced Science. “Until now, dynein has never ever been caught in the business of supplying 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 efficiently stop motility of those cells and, therefore, stop metastatic dissemination.”
Collaborative Efforts and Model Systems
The project began as a collaboration in between Penn States Department of Chemical Engineering and Penn States College of Medicine, before turning into a multi-institution partnership with researchers at the University of Rochester Medical Center, Georgia Institute of Technology, Emory University, and the U.S. Food and Drug Administration.
The most lethal aspect of any cancer is transition, which is the spread of cancer cells throughout the body. Groundbreaking research study led by Penn State has uncovered for the first time the systems that might allow breast cancer cells to attack healthy tissues.” Using these three-dimensional designs that partly simulate a growth, we discovered that if we block the dynein, the cancer cells can not successfully move and infiltrate strong tissues,” Sheikhi said. New research study led by Penn State reveals for the very first time the mechanics behind how breast cancer cells may invade healthy tissues. The discovery, showing that a motor protein called dynein powers the motion of cancer cells in soft tissue designs, offers brand-new clinical targets versus transition and has the possible to basically alter how cancer is dealt with.
Human breast cancer cells are seen moving within a 3D design for healthy soft tissue, created by Amir Sheikhi of Penn State The microgels are undetectable to prevent visual disturbance with the cells. The nuclei of the cells are green. Credit: Erdem Tabdanov/Penn State.
The researchers used live microscopy to see the migration of live breast cancer cells in 2 different systems modeled after the body. The very first system, a two-dimensional network of collagen fibers, exposed how cancer cells move through an extracellular matrix that surrounds tumors and revealed that dynein was essential to the motion of cancer cells.
The 2nd system was a three-dimensional design developed by a group led by Amir Sheikhi, Dorothy Foehr Huck, and J. Lloyd Huck Early Career Chair in Biomaterials and Regenerative Engineering and assistant teacher of chemical engineering and biomedical engineering at Penn State.
Discoveries in Three-Dimensional Models
The second system was designed to imitate soft tissue using a network of microscopic hydrogel particles or microgels connected together in tumor-like shapes. Like in the two-dimensional design, the researchers found in the three-dimensional design that dynein was “indispensable” in the spread or transition of cancer cells.
” Using these three-dimensional models that partially imitate a tumor, we found that if we block the dynein, the cancer cells can not effectively move and penetrate strong tissues,” Sheikhi said. “In both models, we discovered that dynein is incredibly crucial for cell locomotion, which recommends a whole new method for cancer management. Instead of eliminating the cancer cells with radiation or chemotherapy, we are demonstrating how to immobilize them. This is great news due to the fact that you do not truly need to kill the cells, which is a harsh approach that targets both cancerous and healthy cells. Rather, you simply need to stop the cancer cells from moving.”
A human breast cancer cell, adenocarcinoma MDA-MB-231, shows metastatic-like adhesion, spreading and moving in a collagen matrix developed to mimic soft tissue. New research study led by Penn State reveals for the very first time the mechanics behind how breast cancer cells might get into healthy tissues. The discovery, revealing that a motor protein called dynein powers the motion of cancer cells in soft tissue models, offers brand-new clinical targets versus transition and has the prospective to essentially alter how cancer is treated. Credit: Courtesy Erdem Tabdanov
Tabdanov described that cell “paralysis” could prove to be a reliable treatment technique for cancer compared to chemotherapeutic treatments, because after surgical removal of the main tumor, it might prevent the cancer from spreading without destructive healthy tissues and cells.
” The trick with chemotherapy is to eliminate the cancer cells a little quicker than the remainder of the body– its a race against time,” Tabdanov stated. “Chemotherapy causes a lot of damage to the bodys regular, healthy tissues while it is hectic killing the cancer. If we instead consisted of the cancer, stopped it in its tracks, we might keep the healthy parts of the body healthy.”
Future Prospects
The scientists kept in mind that any prospective clinical treatment is still away– as they have yet to run animal or human trials. Sheikhi has filed numerous patents related to his teams platform and prepares to utilize the technology to study a myriad of illness, including other cancers.
” We are really excited about this cooperation with the Penn State College of Medicine, and our labs are working carefully on other tasks,” Sheikhi said. “I believe these platforms might one day make it possible for personalized medicine and personalized treatment for cancer and, hopefully, numerous other illness.”
Recommendation: “Dynein-Powered Cell Locomotion Guides Metastasis of Breast Cancer” by Yerbol Tagay, Sina Kheirabadi, Zaman Ataie, Rakesh K. Singh, Olivia Prince, Ashley Nguyen, Alexander S. Zhovmer, Xuefei Ma, Amir Sheikhi, Denis Tsygankov and Erdem D. Tabdanov, 19 September 2023, Advanced Science.DOI: 10.1002/ advs.202302229.
Other authors on the paper are Yerbol Tagay of Penn State College of Medicine; Sina Kheirabadi and Zaman Ataie of Penn States Department of Chemical Engineering; Rakesh Singh of the University of Rochester Medical Center; Denis Tsygankov of Georgia Institute of Technology and Emory University; and Olivia Prince, Ashley Nguyen, Alexander Zhovmer and Xuefei Ma of the U.S. Food and Drug Administration.
Startup funds from the Department of Pharmacology at Penn State College of Medicine, the Meghan Rose Bradley Foundation, the National Science Foundation, the National Institutes of Health, and the U.S. Food and Drug Administration supported this work.