Researchers have developed a way to mimic the conditions under which cancer tumors grow in bones. By placing cancer cells in a three-dimensional scaffold and subjecting them to the forces that push, pull and continually flow through the body, the researchers are better able to test the efficiency of cancer-fighting drugs.
The scientists discovered that bone tumors exposed to normal forces express more of a protein, insulin-like growth factor-1 (IGF-1), than detected in static cultures. The IGF-1 signaling pathway plays a critical role in resistance to current chemotherapy.
The study, published in the Proceedings of the National Academy of Sciences, shows the value of incorporating mechanical forces when modeling tumors and treatments as opposed to analyzing tumor growth statically, the researchers said.
The researchers specialize in materials and strategies for tissue engineering and regenerative medicine. As part of that work, they have created foam-like materials that serve as scaffolds for cells to inhabit and grow into as they become new bone or tissue.
The researchers placed sarcoma cells in their porous, biologically inert scaffold and put the scaffold inside a flow perfusion bioreactor to mimic the stimulation those cells would experience amid the tissue inside real bone. They subjected the cells to biomechanical stimuli, including shear stress, by changing the fluid viscosity and flow rate.
Over 10 days they found the steady flow of fluid through the scaffold prompted the sarcoma cells to proliferate throughout the structure. The higher shear stress helped the cells significantly increase their production of the IGF-1 protein and also down-regulated the production of two other cancer-related proteins, c-KIT and HER2, compared with static tests.
They also discovered that adjusting parameters in the bioreactor influenced the cells' sensitivity to Dalotuzumab, a drug that disrupts the IGF-1 pathway. Higher shear stress appeared to decrease the drug's effectiveness due to the associated increase in IGF-1 production.
"These experiments have to be tailored for each cancer, because the forces that cells experience vary in different parts of the body. 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," the researchers concluded.
Based on material originally posted by Rice University.