A University of Montana cell biologist has made exciting progress toward finding a way to “program” cancer cells to die rather than to grow.
Mark Grimes, an associate professor in the Division of Biological Sciences, is focusing on neuroblastoma, which is not the most common type of childhood cancer but is the most lethal.
According to 2010 data from the National Cancer Institute, approximately 32 percent of children ages 1 to 14 diagnosed with neuroblastoma died within five years.
That is much better than the 66 percent of children who died in 1975, but much work remains to be done.
Grimes has discovered how to analyze large, complex sets of data to find patterns in the way in which cells interact with each other.
He works at the subcellular level, isolating the molecules that signal cells to divide, die or differentiate.
Since humans are born with more cells than we need to survive, many cells in our bodies are already “programmed” to die. By harnessing the signals in those cells, Grimes said it just might be possible to tell cancer cells to do the same.
“If we can understand the fundamentals of signaling, then we can hope to manipulate these pathways and maybe apply it to neuroblastoma,” he said. “If we can get them to march a little bit further in their differentiation, we could use that differentiation to make each cell susceptible to programmed cell death.”
Grimes recently had his research about the behavior of cell proteins in childhood cancer published in the Public Library of Science Computational Biology.
“On the one hand, we should really acknowledge that great progress has been made, and this paper is a small step in the collective progress many people all over the world have made in understanding cancer – which is many diseases – but we have so much to do,” Grimes said. “One thing we learned is that signal transduction – all of us are composed of cells, and each cell has to respond to its neighbors – all of it is so complicated and what we’ve done find is ways to look for new patterns in this complex data. This is not a solution but a path toward progress.”
The research began because Grimes wanted to understand why cancer cells behave differently than other cells, often metastasizing rather than dying.
He first identified a large number of signaling proteins using mass spectrometry in collaboration with a Massachusetts-based company called Cell Signaling Technology.
However, he collected more data than he knew what to do with.
“I spent an embarrassingly long time staring at a spreadsheet trying to figure out what it all meant,” Grimes said.
So began a five-year immersion in a field that Grimes was previously unfamiliar with: data analytics.
“I felt like Don Quixote for a while, wandering through the wilderness, because I’m really a cell biologist,” Grimes said. “I’m not a statistician. I’m not a computer programmer.”
Working with Dutch pattern-recognition specialist Laurens van der Matten and software engineer Fred Hutchinson, Grimes developed a new analysis technique to calculate relationships in the data.
He discovered that in cancer cells, the components that determine the cell’s behavior – whether it will live, die, migrate or change identity – are functionally compartmentalized into distinct collaborative groups.
Grimes and his research partners at Cell Signaling Technology dissected a large number of neuroblastoma cells to find the specific location of their signaling proteins, and found that two related proteins act like central hubs that distinguish responses to the activation of different receptors.
Grimes hopes that by understanding the fundamentals of cell signaling, scientists eventually might be able to change the signals within cancer cells. For instance, they could trigger cancer cells to die rather than metastasize.
And if this signaling works for neuroblastoma cells, scientists possibly could use the same technology on all cancer cells.
“If we understand how different receptors elicit distinct cell responses,” Grimes said, “we can devise strategies to manipulate cancer cells to cease proliferation, differentiate or commit cell suicide.”
Grimes said he would like for medical researchers to be able to use his data-analysis technique or for computer programmers to create software to utilize it.
“I would encourage students to take math if they are interested in biology to develop quantitative skills to understand statistics and learn how to program computers to understand large data sets,” he said. “We are awash in large data sets. Biology is full of large data sets. It’s not just Google and companies like that. We are getting a lot more data than we can comb through.”
He added that it’s crucial to understand the highly dynamic network of interacting proteins and how they communicate inside the cellular environment to understand the cause of cancer.
“We’ve made tremendous progress on cancer, but we also have to acknowledge we’ve really just sampled a teaspoonful of an ocean full of things we need to do,” he said. “We have a huge amount to do to increase the quality of life, survival and even lifespan. There’s a lot to do on many fronts.”