Understanding how osteosarcoma cells adapt to stress
With long-standing support from the Van Sloun Foundation, our team is studying how osteosarcoma cells adapt to stressful environments and whether these adaptations help tumors survive and spread.
Cancer cells growing in the body face challenges they do not encounter under standard laboratory conditions. In a typical laboratory dish, cells settle onto a flat surface where they can easily attach and have ready access to nutrients. We created a more challenging three-dimensional environment in which the cells must work harder to attach to surrounding proteins, overcome physical forces rather than simply resting on the bottom of a dish, and obtain the nutrients and other resources they need to survive and divide. In effect, we move the cells from a comfortable environment into an obstacle course and ask how they adapt.
We found that osteosarcoma cells respond to this challenge by changing how their DNA is organized. Although the genes themselves do not change, the cells make some regions of their DNA easier to access and use. Many of the genes that become more accessible help cells respond to stress, survive, and move. This led us to ask an important question: Are we recreating in the laboratory some of the same adaptations that help osteosarcoma cells survive the stresses they encounter as they spread through the body?
We are now asking whether these same responses occur in naturally developing osteosarcoma in children and dogs. Using technologies that allow us to examine individual cells and determine where they are located within tissues, we have found that stress responses are not uniform. They occur in particular cell populations and in specific regions of primary tumors and lung metastases. We also see stress responses in non-cancerous lung surrounding metastatic tumors. Human and canine osteosarcomas show similar, although not identical, patterns.
Our next goal is to determine what these stress responses mean for the behavior of the cancer. They may simply help us identify tumors or cells that are more likely to behave aggressively. More importantly, they may reveal weaknesses that we can disrupt to make it harder for osteosarcoma cells to survive, spread, and form metastases.