Research targets formation of esophageal cancer tumors.
An unexpected discovery revealed that esophageal cancer cells do not divide any faster than normal surrounding cells, but they do produce slightly more dividing cells than non-dividing cells, which results in tumor formation.
When it comes to cells, normal cells produce an equal number of dividing and non-dividing cells. An example of this is for every 100 normal cells, 50 will divide and 50 will not; however, in a study published in Nature Cell Biology, the cancer cells showed something different.
For the first time, researchers saw that for every 100 pre-cancer cells, the balance was slightly skewed in favor of dividing cells, with 52 of those cells dividing and 48 that did not. Over time, this slight favoring of cell division can lead to tumor growth.
“We created a new model of human squamous cancer of the esophagus in mice, and measured the rate of cell division,” said lead researcher Philip Jones. “In these mice all the cells in the body divided once per day, proving that precancerous and cancerous cells can divide at the same speed as surrounding normal cells. But the pre-cancerous cells produced a small excess of dividing over non-dividing cells — it was this marginal gain of cells that led to malignant tumors.”
Typically, the balance of dividing and non-dividing cells sustain the tissue, however, tissues can naturally change this ratio in response to certain events, such as a wound that causes an imbalance, but goes back to normal once the wound heals.
In very early tumor tissue development, researchers found that multiple different cells, each with different alterations in their DNA, came together to form a polyclonal pre-cancerous tumor. However, researchers found that as these various pre-tumor cells became cancerous, they would evolve differently, with some gaining an advantage by producing more dividing daughters.
This resulted in a group of cells in the tumor that dominated the other cells.
“Our research showed that esophageal carcinoma and possibly other hard-to-treat cancers may behave in a very similar manner to normal cells, rather than dividing more rapidly,” said lead study author Julia Frede. “This would explain why treatments such as radiation therapy that target fast-dividing cells don’t work with all cancers. More research is needed to find the mechanisms that drive the proportion of cells that divide.”
In the UK, 8750 people are diagnosed with esophageal cancer each year, and it is the sixth largest cause of cancer death worldwide.
“This study, carried out in mice, uncovered surprising evidence that unbalanced cell division is important in the development of a certain type of esophageal cancer,” said Justine Alford, Cancer Research UK’s Senior Science Information Officer. “The next important step will be finding out whether the same is true in patients with the disease. If scientists can unpick the biology causing the imbalance, then I may lead to new treatments for this hard to treat type of cancer and boost the number of people surviving.”