For years, regular physical exams to detect lumps have been one of the frontline diagnostic tools for early detection of breast cancer. But UM-Dearborn bioengineering master’s student Malak Nasser says this palpable hardening of our body’s tissue may be meaningful for a different reason. It may, in fact, be a key part of the way cancer grows and spreads throughout the body.
Malak says this “stiffening” of tissues indicates that the cancer is not only impacting cells in our bodies but the “microenvironments” around the cells. “Basically, there is a mesh that is made up of different proteins around our cells,” Nasser explains. “It affects how the cell grows, it helps the cells attach and stay in place, all sorts of things. And the cells can also sense changes in this mesh and react accordingly.” And when we’re able to feel a lump, it’s because of the stiffness of this mesh.
This mesh microenvironment is of particular interest to cancer researchers because cancer is, in essence, an uncontrolled growth of cells. To support this growth, they find ways to redirect the body’s vital nutrients, often via blood vessels , which means they need some mechanism for communicating. Nasser’s hypothesis: This hardening of the mesh microenvironment may actually be helping cancer cells send out signals to the body to keep oxygen and other nutrients heading their way.
To test this hypothesis, Nasser first recreated a simplified version of this microenvironment using a gel-suspend collagen — one of the key proteins in our body’s natural extracellular mesh. She then inserted human breast cancer cells into several different versions of these collagen environments, which varied in their degree of “stiffness.” Finally, she tested whether the stiffness impacted the cancer cells' signaling ability. Specifically, she was looking for signals that promote or inhibit a process called angiogenesis. That’s our body’s mechanism for making new blood vessels, which cancer cells often harness to maintain a steady stream of nutrients.
When she analyzed her results, the trendline was clear: Basically the stiffer the environment, the greater the increase she saw in signals related to angiogenesis.
Interestingly, Nasser says that finding points to some ideas for clinical treatments: “If we know that increased stiffness is causing the release of more angiogenesis-related signals, then what if we inhibit the ability of the cells to sense this stiffness change? Would this help decrease the amount of signals they released, and ultimately help slow down the ability of the cancer to grow and spread throughout the body?”
Nasser is investigating that hypothesis now in a second phase of her master’s thesis work. In an experiment similar to her first, she’s testing several different signal-inhibiting drugs in “stiff” environments, to see which inhibitor may be the most effective. After she concludes that work, she plans to design similar experiments for bone tissue. For that, she’ll actually be using a bio 3D printer to create mineralized environments that mimic the harder microenvironment mesh found in our bones.
For her work, Nasser took home the top prize in UM-Dearborn’s recent Three Minute Thesis (3MT) competition — an annual event that challenges graduate students to present their research in compact, engaging and understandable ways. Students from more than 200 universities compete in the 3MT every year. Nasser’s win at UM-Dearborn earns her a ticket at the regional 3MT competition, which is currently postponed due to the coronavirus pandemic.
