Cancer cells become more aggressive when exposed to stiffening tissues and these changes persist over time, according to a new study by health scientists at the University of Arizona. The article titled “Breast tumor stiffness instructs bone metastasis via maintenance of mechanical conditioning,” published in the journal Cell Reports, found that the stiffness of the breast tumor microenvironment can lead to changes in cancer cells. which make them more aggressively spread to the bone.
Tumor stiffening, which develops as diseased breast tissue becomes fibrous, plays a major role in the spread of breast cancer cells throughout the body. The resulting changes are stored in the form of “mechanical memory,” which asks cancer cells to send signals that lead to bone breakdown. Once this happens, patients often suffer from debilitating complications like spontaneous fractures.
“Unfortunately, bone metastases are normally only identified at an advanced stage where they are not reversible,” said lead author Ghassan Mouneimne, PhD, associate professor of cellular and molecular medicine and cancer biology at the University of Arizona College of Medicine – Tucson. He added: “What’s really exciting is that one day we can take a sample from the patient’s primary tumor and predict who is at high risk for bone metastasis. Then we could intervene with a prevention strategy that we are currently validating in the laboratory. “
The study, which is the first to demonstrate the concept of mechanical memory in cancer metastases, developed a new mechanical conditioning score, or “MeCo”, to quantify cellular changes. Ultimately, the researchers hope the MeCo score can be used to help identify breast cancer patients who might benefit from reused antifibrotic treatments to prevent bone metastasis. “The higher the MeCo score of the patient’s breast tumor, the greater the likelihood of her having metastasized to bone and poorer outcomes,” said Casey Romanoski, PhD, assistant professor of cellular and molecular medicine and member of the BIO5 Institute and the University of Arizona Cancer Center. “This stiffness signature could have incredible clinical utility.”
To further explore the clinical application, Dr. Mouneimne and Adam Watson, PhD, a former graduate student and postdoctoral fellow at the University of Arizona Cancer Center, worked with Tech Launch Arizona, the university’s office that commercializes inventions from the research, to launch a startup, MeCo Diagnostics, LLC. The company strives to mature the technology and bring it to market where it can impact the lives of breast cancer patients around the world.
It was previously known that tumor stiffness induces cellular changes that lead to more aggressive cancer, but according to lead author Dr. Watson, the concept of “stiffness” was misleading. “Most early-stage breast tumors are stiffer than the surrounding tissue, but most don’t spread to bone,” he said. “It’s not about tumor stiffness but rather reactivity to the stiffness of cancer cells, which we call mechanical conditioning.”
To study this phenomenon, the team created a laboratory environment that mimicked the rigid or soft tumor environments found in the body and assessed the response of breast cancer cells. They found that cells grown in a rigid environment had a “mechano-response” characterized by the spread, invasion and activation of genes related to both bone development and disease. And these genetic changes persisted even after the cells were moved to a mild environment.
Next, the researchers looked at which genes were turned on and off in breast cancer cells in response to the harsh environments. Based on these gene expression changes, they developed the MeCo score, which has been validated and refined using data from thousands of breast cancer patients. “It is the culmination of a lot of work by researchers from many different fields,” said Dr Mouneimne. “It highlights the environment we have at the Arizona University of Health Sciences, and how working together can make progress in this difficult area of breast cancer metastasis.”
Future research may focus on how cancer cells maintain gene expression changes that lead to metastasis, based on additional findings that identified a transcription factor called RUNX2 that was activated by fibrotic-like stiffness. . RUNX2 stays attached to DNA as the cell divides and “tags” which genes stay on, which includes genes that cause bone metastasis and bone breakdown. (ANI)
(This story was not edited by Devdiscourse staff and is auto-generated from a syndicated feed.)