Geoffrey Wertime

By: centraljersey.com
Researchers from Princeton University have discovered new aspects to a type of cell, and they say their findings may one day lead to a treatment for diseases including cancer and HIV.
The work focused on cells called fibroblasts that can be found in connective tissue and which serve as structural framework and in helping wounds heal. The traditional view has held that when they go into a state called quiescence, the cells shut down, but in Tuesday’s edition of the journal PloS Biology, the university’s team revealed that’s not the case.
"I didn’t actually think (the traditional view) was wrong when we started out," said Hilary Coller, an assistant professor of molecular biology. But through her research with colleagues, she said they discovered "sleepy" quiescent fibroblasts are actually busy putting material into the extracellular matrix, the biological "glue" that keeps cells bound in tissues. The quiescent cells also rely on a chemical process that fights free radicals – misprocessed oxygen that can interfere with the body’s proteins.
But Dr. Coller said the most exciting discovery is the cells’ use of what’s called the pentose phosphate pathway, a process which transforms glucose in the body into ribose, a key ingredient in the body’s production of nucleic acids like DNA.
"The thing that’s really exciting is that if you inhibit the pentose phosphate pathway in quiescent cells, they die. And this is a big deal because they’re like little supermen," she said.
Quiescent cells are considerably harder to kill than active cells, she explained, and can often withstand serious mistreatment like hydrogen peroxide. Diseases like cancer and HIV make use of these cells by keeping part of themselves locked away in quiescence, Dr. Coller said while it’s known they sometimes reemerge at a later date, no one knows why.
Blocking the pathway in those dangerous cells could theoretically kill cancer, she explained. The possibility is particularly exciting because current treatments, like chemotherapy, target the cells that divide the fastest.
"Most chemotherapy regiments are specifically effective against dividing cells, and that’s great for the mass because it’s dividing," Dr. Coller said. But that approach misses the quiescent cells, which could allow the disease to return at a later date.
But first, other researchers will need to find a way to target those cells while leaving regular, undiseased quiescent cells untouched.
"I worry about that," Dr. Coller said, but she added she had found encouraging research at other institutes.
She mentioned two possible approaches to the problem. One would involve genetically engineering a bacteria that can survive with very little oxygen to seek out these dense, diseased quiescent cells and block the pathway in only those cells. Alternately, work is already underway with nanotechnology, or the use of extremely small constructs, that could target the cells in question.
"If we got really good at quiescent cells, it may well be a way to target tumors," Dr. Coller said. "We have a long way to go, and we’re still working, but our immediate plans are to extend (our research)."
Another aspect of the research could apply to HIV. That disease’s ability to hide in quiescent cells is what makes it impossible for current science to cure, Dr. Coller said. While the pentose phosphate pathway doesn’t look like the right approach to stopping it, she said she hopes other findings in the paper will lead to another way to eradicate the disease and she’ll continue to pursue them.
"We’re hopeful we’ll have more insights that are helpful in understanding how to get rid of HIV reservoirs," she said.
Next up, Dr. Coller said the team will look at other types of fibroblast cells, and then will investigate lymphocytes, a type of white blood cells, to see if they, too, use the pentose phosphate pathway. She also said she hopes to partner with the Cancer Institute of New Jersey in New Brunswick as the research moves forward.
"Obviously we’re excited to do work on cancer stem cells," Dr. Coller said, referring to what are thought to be the quiescent cancer cells. While this type of work takes time, she said, "we’re in a rush and hope in a couple of years we’ll have great results" in trials with mice.
Other authors on the paper included Johanna Lemons, a graduate student in chemistry and first author on the article, and Joshua Rabinowitz, an associate professor of chemistry with whom Ms. Lemons also worked.
[email protected]