Two researchers at the University of Massachusetts have received a three-year, $425,000 grant from the National Science Foundation to study cancer that has spread, or metastasized, into bones from other organs in the body.
The research team of Maureen E. Lynch and Yahya Modarres-Sadeghi will focus much of their research on breast cancer, because roughly three in four patients with advanced breast cancer develop incurable bone metastases, or growths. Once bone metastasis occurs, the prognosis for the patient declines dramatically, due to complications, including bone destruction.
Lynch is an assistant professor of mechanical and industrial engineering, Modarres-Sadeghi is an associate professor in the same department.
The skeleton is the preferred site for metastasis in many cancers, including breast, prostate, lung and kidney. The spread of cancer to the skeleton is common, yet incurable. The goal of the research is to define for the first time how the mechanical signals arising from physical activity, the primary regulator of bone cell function, affect the bone metastatic cells when they are exposed to these same signals.
“After metastasis occurs, patient prognosis dramatically declines due to severe skeletal-related complications, including bone destruction,” Lynch and Modarres-Sadeghi say in a press release. “Mechanical signaling, which results from physical activity imparting forces on the skeleton, is inherent to the bone microenvironment and is critical for healthy bone remodeling. Though metastatic cancer cells are exposed to these same signals when they arrive in the skeleton, their role in metastasis in unclear.”
Bone remodeling is the ongoing process where the body removes old bone tissue and replaces it with new, stronger bone tissue.
The researchers say that once metastatic tumor cells spread to the bones, these tumor cells interrupt the normal bone remodeling process and initiate bone destruction by releasing material from the bone matrix that will “feed” the tumor cells.
Currently, the standard of care for this condition is drugs that merely slow metastatic progression, but they do not recover lost bone. The researchers believe that additional factors and cell types are likely promoting bone metastasis, highlighting a lack of fundamental understanding of the mechanisms that underlie bone metastatic tumor initiation and progression.
Lynch and Modarres-Sadeghi seek to systematically define the functional relationship between mechanical signals and bone metastatic cell function.
“The results of this project will transform our fundamental understanding of how tumor cells are regulated in the skeletal microenvironment with considerable potential to improve clinical management of the disease,” say Lynch and Modarres-Sadeghi. “The data collected from these studies will form the foundation for defining the role of mechanical stimulation during bone metastasis.”