The past few months have reminded us of how important it is to stay connected with others. As humans, we need other people to support us through challenges, to strengthen us when we are weak, and to guide us when we are lost.
These connections help us outlast the unimaginable, but what would it mean if a cancer cell was able to connect? What if cancer cells built their own support network to help them survive cancer treatments? Some cancers are able to do just that. In our research laboratory, we study the processes and structures that build these networks in brain cancer.
Glioblastoma is the most common and most aggressive type of brain cancer in humans. Glioblastoma carries a very bad medical prognosis and this cancer’s ability to draw support from neighboring cancer cells is part of what makes it so difficult to treat.
Glioblastoma cells build unique structures called tumor microtubes that extend far away from the cancer cells in many directions, like the tentacles of an octopus. When these tentacles connect with other glioblastoma cells, they can act like a bridge that allows the direct transfer of cellular resources. This exchange supports the continued growth of cancer cells that otherwise may not survive.
Tumor microtubes also help glioblastoma cells move into new parts of the brain by functioning like antennas. At the edge of the tumor, they extend out into the normal brain tissue to find the best path forward. Once a direction is identified, tumor microtubes can guide the movement of cancer cells away from the main tumor mass.
As the tumor grows, more glioblastoma cells invade further into the brain and are bridged together. This causes the network of connected cancer cells to becomes larger and extend far beyond the edge of the visible tumor. As a result, even tumors that are surgically removed leave behind many invisible cancer cells that are interconnected and scattered throughout the brain.
Cancer cells that are left behind after surgery are usually treated with radiation and chemotherapy. With treatment, glioblastoma may retreat for a short while, but the glioblastoma cells that survive this treatment eventually become resistant to these and all other known treatments. The cause of this resistance is complex, but we know that tumor microtube networks help glioblastoma cells withstand and survive treatment.
Radiation and chemotherapy are useful cancer treatments because they are toxic to growing cells. While individual cancer cells are sensitive to this toxicity, glioblastoma cells that are bridged together by tumor microtubes can distribute the toxicity amongst a large network of cells. Just like a person relying on a network of support in a crisis, sharing toxic stress lessens the burden on each individual cell and helps connected cancer cells to survive treatment.
Our research lab is investigating drugs that collapse and prevent these glioblastoma cell networks. Our goal is to make glioblastoma cells more sensitive to radiation and chemotherapy treatments by removing the survival advantages provided by these cellular connections. Our drugs could also be explored to treat other cancers that build and benefit from similar networks, but the number of cancers that form these connections is likely underestimated.
Cancer researchers often use established samples of human tumor cells that have grown in a laboratory dish for many years. Growing cancer cells in a laboratory dish has many advantages, but this artificial environment is very different than the environment within the human body. Over time, cells grown in a laboratory dish can and do change in response to this altered environment, making it even more challenging to develop drugs that will work in human bodies.
Our lab collaborates with Toledo area brain surgeons and glioblastoma patients to solve this problem by isolating cancer cells directly from patient tumor samples. These donated tissue samples allow us to study cancer cells just days after they were last growing in the human body and before they are able to change in a laboratory dish. With this approach, we are able to learn things about glioblastoma that are more likely to apply to real patients. This collaboration also allows us to compare what we see in the lab with the behavior of the tumors in real patients. Most cancer researchers are not using this type of cancer cell model, but it was only after we began to work with patient cells that we started to observe tumor microtubes and their networks.
Without the patients and families that generously donate their tumors to our research program, we could not study these cancer cell networks or the ways that they block the successful treatment of brain cancer. The Eisenmann Lab is grateful and dedicated to the opportunities and responsibilities that come with these gifts.
We believe that our work highlights the ways in which, like many other things, progress in cancer research depends on the community for support.
Kathryn Becker is currently an M.D./Ph.D. student in the Department of Cancer Biology at The University of Toledo College of Medicine and Life Sciences Biomedical Science Program. Kathryn is doing her research project in the laboratory of Dr. Kathryn Eisenmann. For more information, contact Kathryn.Becker@rockets.utoledo.edu or go to utoledo.edu/med/grad/biomedical
First Published July 6, 2020, 1:32 p.m.
