DDNews Cancer Research Exclusive: Communication is key

MU researchers seek to harness bacterial communication molecules that could target cancer cells

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COLUMBIA, Mo.—Bacteria are perhaps the last things people would think would be helpful in the face of cancer—indeed, bacterial infections, which cancer patients are prone to as their immune systems are weakened by cytotoxic chemotherapy, are a significant concern for those undergoing cancer treatments. But new research into the way bacteria communicate within their colonies has revealed that a communication molecule could serve to keep cancer cells from metastasizing. The study, “Bacterial Quorum Sensing Molecule N-3-Oxo-Dodecanoyl-L-Homoserine Lactone Causes Direct Cytotoxicity and Reduced Cell Motility in Human Pancreatic Carcinoma Cells,” was published in PLOS ONE on Sept. 14.

Senthil Kumar, an assistant research professor, assistant director of the Comparative Oncology and Epigenetics Laboratory at the University of Missouri College of Veterinary Medicine and lead author of the study, added that “During an infection, bacteria release molecules which allow them to ‘talk’ to each other. Depending on the type of molecule released, the signal will tell other bacteria to multiply, escape the immune system or even stop spreading. We found that if we introduce the ‘stop spreading’ bacteria molecule to cancer cells, those cells will not only stop spreading; they will begin to die as well.”
As explained in a paper titled “Quorum sensing in bacteria,” which appeared in the Annual Review of Microbiology in 2001, “Quorum sensing is the regulation of gene expression in response to fluctuations in cell-population density. Quorum sensing bacteria produce and release chemical signal molecules called autoinducers that increase in concentration as a function of cell density ... Gram-positive and Gram-negative bacteria use quorum sensing communication circuits to regulate a diverse array of physiological activities. These processes include symbiosis, virulence, competence, conjugation, antibiotic production, motility, sporulation and biofilm formation.”
“The bacteria in a colony communicate within each other,” Kumar explains. “Based on that, they decide whether to multiply, to infect the whole organism or whether to evade the immune system, and so on and so forth. So they secrete these molecules into the colony where they are infested, and then they will detect those compounds and take it back inside, and then it controls the gene expression, based on the concentration of this compound.”
Based on that, he says, they thought that perhaps applying this system to cancer cells could serve to control proliferation, migration or metastases.
The researchers treated human pancreatic cancer cells grown in culture with bacterial communication molecules known as O-DDHSL (oxo-dodecanoyl-L-homoserine lactone). After being treated with these molecules, the cancer cells not only stopped proliferating, they no longer migrated and began to die as well. Jeffrey Bryan, an associate professor in the MU College of Veterinary Medicine, was co-author for this paper.
“We used pancreatic cancer cells because those are the most robust, aggressive and hard-to-kill cancer cells that can occur in the human body,” Kumar said in a press release. “To show that this molecule can not only stop the cancer cells from spreading, but actually cause them to die, is very exciting. Because this treatment shows promise in such an aggressive cancer like pancreatic cancer, we believe it could be used on other types of cancer cells, and our lab is in the process of testing this treatment in other types of cancer.”
Moving forward, Kumar says he and his colleagues are pursuing a number of different avenues, including the search for a more efficient way to get the communication molecules to cancer cells. Attaching the molecules to antibodies is one possibility, though Kumar notes that that the problem with that approach is that “you cannot manipulate the compound too much without compromising the integrity.” They also want to ensure that this approach isn't toxic to normal cells.
“We don't want to go systemic at this point, because we don't know what it does systemically in the animals,” he explains. “If it's causing unnecessary toxicity it's going to be a problem, but we believe it may not, because it itself is not a toxin, it is just a communicating molecule.”
“Our biggest challenge right now is to find a way to introduce these molecules in an effective way,” Kumar concluded. “At this time, we only are able to treat cancer cells with this molecule in a laboratory setting. We are now working on a better method which will allow us to treat animals with cancer to see if this therapy is truly effective. The early-stage results of this research are promising. If additional studies, including animal studies, are successful then the next step would be translating this application into clinics.”

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