In a joint study researchers at NYU Langone Medical Center, the Dana Farber Cancer Institute at Harvard, and the University of Michigan Medical School have uncovered fascinating information about how pancreatic cancer cells avoid starvation: They force nearby support cells to provide them with sustenance. The study reveals that pancreatic cancer is a world class scavenger, and can stay alive when its usual fuel (food) oxygen and glucose are scarce in the body’s bloodstream.
According to the study, pancreatic cancer cells transmit a message to Pancreatic Stelle Cells (PaSCs or PSCs) which reside in the exocrine area of the pancreas. When they are activated by the body they head to the area of injury and are involved in tissue repair secreting ECM components. Pancreatic cancer cells tell the pancreatic steele cells to begin to secrete substances that give them structural support. Thus they breakdown, and in the wake of that breakdown pancreatic cancer cells swoop in and a take up the alanine released by the pancreatic stele cells, using it as a fuel source to replace the scarce glucose.
In essence; pancreatic cancer cells transmit a secretion command message to pancreatic stele cells, and when those stelle cells do as instructed by the pancreatic cancer cells the obedience to that command allows the pancreatic cancer cells to feed.
The study offers solid proof that pancreatic cancer uses fuel-food in a manner very different from others types of cancers, but that pancreatic cancer is a master scavenger in times of fuel-food scarcity when compared to other cancers. By establishing the existence of communication between tumors and stelle cells there is a foothold to begin to create drugs that will disrupt this communication, similar to jamming a radio signal.
To crux of the experiment was to observe how pancreatic cancer cells continue to grow in a scarce fuel-food situation with the premise that it was stelle cells feeding the cancer. In their observations researchers noted that when stellate cells were secreting metabolites there was a 20% to 40% increase in the mitochondrial metabolism taking place inside cancer cells. Taking all 200 metabolites observed into account, they then identified that alanine was the only amino acid that had a quantifiable effect on the cancer cell propagation and metabolic mitochondrial activity.
The next course of action was the determination of the manner in which cancer cells used alanine. Tagged carbon molecules that composed alanine proved pancreatic cancer cells were converting alanine and using it to produce energy within the mitochondria. By using this secondary food source for basic energy production this freed up primary fuel-food such as glucose to be used in crucial areas like DNA structure with the cancer cell. Additionally the researchers found the cancer cells released an as yet unidentified substance could force stelle cells to increase the amount of alanine by stimulating autophagy. Autophagy protects damaged cells inside vesicles in which proteins and fats are transformed into metabolites and then turned into new DNA strands and membranes. All of which are paramount to the proliferation of cancer cells.
Taking all this data and discovery into account the researchers then tested their theory in mice by monitoring tumor growth. Alanine secretion hinges on autophagy, thus focused disruption was possible to by genetic manipulation of the stelle cells in the test mice. The outcome: Autophagy was halted, alanine secretions restrained, and tumor growth was minimal.
The next steps will be to attempt to develop drugs to replicate that process, and thus be utilized to block cancer cells from communicating with stelle cells and utilizing them for fuel-food.