A collaborative effort between Rice University and University of Texas MD Anderson Cancer Center (both TX, USA) has enabled researchers to develop a way to mimic the conditions that facilitate tumor growth in bones.
Recently published in the Proceedings of the National Academy of Sciences, the authors assert that their findings demonstrate the value of incorporating mechanical forces during the modeling of tumors and treatments as opposed to analyzing tumor growth statically.
For the research, sarcoma cells were placed in a porous, biologically inert 3-dimensional bioscaffold and were placed in a flow perfusion bioreactor to recreate the biomechanical stimuli, including shear stress, which the body routinely experiences. This enabled the researchers to test the efficiency of cancer-fighting drugs.
It was discovered that bone tumors exposed to standard forces experienced by the body express higher levels of insulin-like growth factor-1 (IGF-1) than static cultures. The IGF-1 signaling pathway is known to play a critical role in resistance to current chemotherapy treatments.
“Mechanical forces are present in our bodies even though we are not always aware of them,” explained author Antonios Mikos (Rice University). “Our cells are sensitive to the forces around them and change their behavior accordingly. Tumor cells behave the same way, changing their function depending on the forces they sense.”
Over 10 days, the researchers discovered that a steady flow of fluid through the scaffold prompted the sarcoma cells to proliferate throughout the structure. Increased shear stress induced a significant increase in the production of IGF-1 and also downregulated the production of c-KIT and HER2, compared with static tests. It was also discovered that the sarcoma cells sensitivity to dalotuzumab could be influenced by the adjustment of bioreactor parameters. Increased shear stress appeared to decrease the effect of dalotuzumab due to the associated increase in IGF-1 production
“For the first time, we showed how the effect of the drug changes according to the forces experienced by the cells,” lead author Marco Santoro commented. “IGF-1 is crucial for this kind of sarcoma, which relies on this mechanism for growth. We show that the higher the mechanical stimulation, the more pronounced the secretion of this particular protein.”
Mikos stated that the experiments should set a good example for studies of other cancers. “These experiments have to be tailored for each cancer, because the forces that cells experience vary in different parts of the body,” he explained. “In the lungs, they wouldn’t be the same as in the bones. But they give researchers a far more realistic way to mimic the tumor’s local environment.”