Cancer metastasis is a difficult stage to battle, especially if cancer cells are proliferating at a rapid pace. A new study reveals that metastatic cells change their shape to spread to other parts of the body. Researchers formulated a mathematical model to study metastatic cell behavior and similar cellular systems.
Defining tumor stage at diagnosis is an imperative phase for clinical decisions about treatment approaches. Hence, early detection of hidden metastasis that can’t be detected by imaging methods would greatly impact treatment strategies and long-term survival.
The team of researchers at Beth Israel Deaconess Medical Center crafted a mathematical framework to understand the dynamics of how tumor cells grow and spread. The model is helpful to simplify complex systems for better understanding of physiological dynamics of body processes.
Migrating cancer cells. Image Credit: Juan Gaertner / Shutterstock
Metastasis and how it works
Metastasis involves the movement or spread of tumor cells from one tissue or organ to another. The cancer cells break away from the tumor origin and form new tumors in another part of the body. They travel through the blood or the lymphatic system.
The metastatic cancer cells cross the endothelium, a group of cells that line the circulatory system and they control the passage of material into and out of the bloodstream. Crossing over the endothelium isn’t a characteristic of non-metastatic cells.
Metastasis happens when cancer cells spread through the body. First, it invades nearby healthy tissues and moves to nearby blood vessels or lymph nodes. From there, they travel through the bloodstream or lymphatic system to other organs of the body.
They invade blood vessel walls and move into nearby tissues. In the location of metastasis, the tumor cells start to grow in the tissue to form tiny tumors, triggering new blood vessels to form to create a stable supply of blood and nutrients. This allows the tumor to continue growing.
Cancer metastasis is a multifaceted process involving changes in certain mechanochemical, genetic, and environmental levels. Since it’s complex, a mathematical framework may help copy, quantify, and characterize tumor behavior.
Numbers can quantify the interaction between metastatic and endothelial cells
Published in the journal Scientific Reports, the study reveals that unlike non-metastatic cells, breast metastatic cells can change their shape, becoming flat to be able to cross the endothelium and into the bloodstream. The mathematical formula or model can quantitatively show what happens between the metastatic cells and the endothelial cells.
Both the metastatic cells and endothelial cells go through physical changes that are important for metastasis to occur. For instance, breast epithelial cells reduce the stiffness of endothelial cells to promote epithelial cell transmigration, and at the same time, flatten their shape to easily pass through the endothelium.
Also, metastatic cells are 80 percent more yielding than benign cells. This reduction in cell stiffness and toughness may enhance the ability of cancer cells to cross the barrier and into the bloodstream.
"Our data show that breast metastatic cells are not only able to find blood vessels more effectively, but they also are able to change their shape to help facilitate crossing into the bloodstream, which is a critical step in the spread of cancer,” Dr. Yamicia D. Connor, a resident in the Department of Obstetrics and Gynecology at Beth Israel Deaconess Medical Center, explained.
"The study demonstrates how mathematical models can be paired with biological systems to provide and quantify important insights in cellular biology and potentially test drug targets,” she added.
New hope to study metastatic cell behavior
The mathematical model can help researchers and doctors to study the behavior of metastatic cells. At the same time, they can investigate whether the behavior is limited only to breast cancer cells or it can be applied to other metastatic cancers.
The framework can shed light on the mechanism of metastatic disease, and in the future, can be used to guide treatment approaches and decisions.
Cancer is among the leading causes of death across the globe. There were 14.1 million new cases and 8.2 million cancer-related deaths worldwide in 2012. By 2030, experts project that the number of new cancer cases each year will increase to 23.6 million.
The most common cancer types include liver cancer, thyroid cancer, pancreatic cancer, leukemia, endometrial cancer, renal cancer, non-Hodgkin lymphoma, bladder cancer, melanoma, colon cancer, prostate cancer, lung cancer, and breast cancer.
A mathematical model of tumor-endothelial interactions in a 3D co-culture, Yamicia Connor, Yonatan Tekleab, Sarah Tekleab, Shyama Nandakumar, Divya Bharat & Shiladitya Sengupta, Scientific Reportsvolume 9, Article number: 8429 (2019), http://dx.doi.org/10.1038/s41598-019-44713-2 , https://www.nature.com/articles/s41598-019-44713-2