Cancer researchers looking for a breakthrough might want to relocate to the International Space Station. Biologists have found that microgravity research and other space-based experiments provide greater insight into abnormal cell behavior.
In Earth-bound labs, cells grow flat, unable to fully mimic the three-dimensional architecture shaped by proteins and carbohydrates of a working human organ. This gap provides an obstacle for scientists studying changes in cell growth and development.
In space, cells clump together easily, arranging themselves into three-dimensional groupings that better replicate cell activity. They also experience less fluid shear stress, a type of disturbance that affects their behavior outside of the body.
Many of the cells in space will likely die due to a lack of blood vessels providing necessary oxygen and nutrients. That might seem like a disadvantage, but it actually resembles the condition of tumors with areas of dead tissue at their centers, biologists say.
The Cellular Biotechnology Operations Support System (CBOSS-1-Ovarian) investigation, located aboard the space station, contains a cell incubator that grows 3-D clusters of cells. These structures have enhanced the ability of researchers to understand protein production, a key element of cell behavior.
Jeanne Becker, Ph.D., a cell biologist at Nano3D Biosciences in Houston and principal investigator for the CBOSS-1-Ovarian study, recently authored a paper that examined cell biology research in microgravity from the past four decades.
"So many things change in 3-D, it's mind-blowing -- when you look at the function of the cell, how they present their proteins, how they activate genes, how they interact with other cells," Becker said in a statement. "The variable that you are most looking at here is gravity, and you can't really take away gravity on Earth. You have to go where gravity is reduced."
Among the studies covered in the paper: one investigation conducted on the Columbia space shuttle in 1998 revealed cultured cells with altered genetic expressions. The results of another space-based experiment indicated that microgravity suppresses the immune system.
While the unique physical conditions of space have proven apt, research on Earth is also making headway with the construction of 3-D cell structures using a collagen gel matrix. Combined with microgravity studies, such research advances could greatly help biologists understand the cellular changes that lead to cancer and develop ways to prevent them.
"...Chemical That Makes Naked Mole Rats Cancer-Proof Discovered
June 19, 2013 — Two researchers at the University of Rochester have discovered the chemical that makes naked mole rats cancer-proof.
146The findings could eventually lead to new cancer treatments in people, said study authors Andrei Seluanov and Vera Gorbunova. Their research paper will be published this week in the journal Nature.
Naked mole rats are small, hairless, subterranean rodents that have never been known to get cancer, despite having a 30-year lifespan. The research group led by Seluanov and Gorbunova discovered that these rodents are protected from cancer because their tissues are very rich with high molecular weight hyaluronan (HMW-HA).
The biologists' focus on HMW-HA began after they noticed that a gooey substance in the naked mole rat culture was clogging the vacuum pumps and tubing. They also observed that, unlike the naked mole rat culture, other media containing cells from humans, mice, and guinea pigs were not viscous.
"We needed to understand what the goo was," said Seluanov.
Gorbunova and Seluanov identified the substance as HMW-HA, which caused them to test its possible role in naked mole rat's cancer resistance.
Seluanov and Gorbunova then showed that when HMW-HA was removed, the cells became susceptible to tumors, confirming that the chemical did play a role in making naked mole rats cancer-proof. The Rochester team also identified the gene, named HAS2, responsible for making HMW-HA in the naked mole rat. Surprisingly, the naked mole rat gene was different from HAS2 in all other animals. In addition the naked mole rats were very slow at recycling HMW-HA, which contributed to the accumulation of the chemical in the animals' tissues.
The next step will be to test the effectiveness of HMW-HA in mice. If that test goes well, Seluanov and Gorbunova hope to try the chemical on human cells. "There's indirect evidence that HMW-HA would work in people," said Seluanov. "It's used in anti-wrinkle injections and to relieve pain from arthritis in knee joints, without any adverse effects. Our hope is that it can also induce an anti-cancer response."
"A lot of cancer research focuses on animals that are prone to cancer," said Gorbunova. "We think it's possible to learn strategies for preventing tumors by studying animals that are cancer-proof."
Previous research by Seluanov and Gorbunova showed that the p16 gene in naked mole rats stopped the proliferation of cells when too many of them crowd together. In their latest work, the two biologists identified HMW-HA as the chemical that activates the anti-cancer response of the p16 gene.
The research was supported by grants from the U.S. National Institutes of Health and the Ellison Medical Foundation.
Hyaluronan (HA), which makes tissues supple and aids in the healing process, is found in high concentrations in the skin of naked mole rats. The biologists speculate that the rodents developed higher levels of HA in their skin to accommodate life in underground tunnels.
Future research from the Gorbunova and Seluanov labs will focus on determining whether the HMW-HA from naked mole rats may have clinical value for either treating or preventing cancer in humans..."
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