For years, regular physical exams to detect lumps have been one of the frontline diagnostic tools for early detection of breast cancer. But 萝莉社-Dearborn bioengineering master鈥檚 student Malak Nasser says this palpable hardening of our body鈥檚 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 鈥渟tiffening鈥 of tissues indicates that the cancer is not only impacting cells in our bodies but the 鈥渕icroenvironments鈥 around the cells. 鈥淏asically, there is a mesh that is made up of different proteins around our cells,鈥 Nasser explains. 鈥淚t 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.鈥 And when we鈥檙e able to feel a lump, it鈥檚 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鈥檚 vital nutrients, often via blood vessels , which means they need some mechanism for communicating. Nasser鈥檚 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 鈥 one of the key proteins in our body鈥檚 natural extracellular mesh. She then inserted human breast cancer cells into several different versions of these collagen environments, which varied in their degree of 鈥渟tiffness.鈥 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鈥檚 our body鈥檚 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: 鈥淚f 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?鈥
Nasser is investigating that hypothesis now in a second phase of her master鈥檚 thesis work. In an experiment similar to her first, she鈥檚 testing several different signal-inhibiting drugs in 鈥渟tiff鈥 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鈥檒l 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 萝莉社-Dearborn鈥檚 recent Three Minute Thesis (3MT) competition 鈥 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鈥檚 win at 萝莉社-Dearborn earns her a ticket at the regional 3MT competition, which is currently postponed due to the coronavirus pandemic.
