As MesotheliomaHelp has reported time and again, the spread of cancer cells, or metastasis, is the biggest challenge for researchers when searching for effective treatments. It is this migration of the cancer cells, according to the National Cancer Society, that is the cause of 90 percent of all cancer deaths. Stopping this spread is critical for improving survival in mesothelioma patients. Now, researchers report they have found the reason cancer cells split off from the primary site, and more importantly, they may also know how to stop the process.
In a May 26 press release from Johns Hopkins, lead researcher Hasini Jayatilaka, a postdoctoral fellow at Johns Hopkins’ Physical Sciences-Oncology Center, found that it is not the overall size of a tumor that leads to metastasis, rather “how tightly those cells are jammed together” that has them break away. Jayatilaka likened the process to waiting for a table in an overcrowded restaurant but then deciding to go elsewhere or moving to the suburbs from the crowded city.
Cancer cells metastasize because they can reproduce quickly and they can get into the bloodstream where they then spread to other organs. When looking deeper into those processes, the team found that when the tumors became “more crowded” the cells secreted proteins that “encouraged migration.” The proteins, Interleukin 6 (IL-6) and Interleukin 8 (IL-8), sent signals basically telling the cancer cells to leave the primary tumor site.
“We found that it was not the overall size of a primary tumor that caused cancer cells to spread, but how tightly those cells are jammed together when they break away from the tumor,” said Jayatilaka. “At a fundamental level, we found that cell density is very important in triggering metastasis.”
When the researchers used two existing drugs at the tumor site, one approved for treating arthritis and the other being tested for breast cancer treatment, the receptors were blocked from receiving those signals, effectively halting the metastasis. Although the growth at the primary tumor site did not stop, the spread of the cancer cells was limited. This helped confirm that by blocking the signaling pathway, they could slow metastasis.
Expert Insight“This treatment has the potential to inhibit metastasis and thus improve cancer patient outcomes.”
“In our eight-week experiment, when we used these two drugs together, the growth of the primary tumor itself was not stopped, but the spread of the cancer cells was significantly decreased,” Jayatilaka said. “We discovered a new signaling pathway that, when blocked, could potentially curb cancer’s ability to metastasize.”
Once mesothelioma cells spread to distant regions of the body, the cancer, caused by past asbestos exposure, becomes virtually impossible to eradicate. Getting a handle on the spread of cancer is critical for increasing survival.
“The pharmaceutical companies view metastasis as a by-product of tumor growth,” said Denis Wirtz, Johns Hopkins University’s vice provost for research and director of its Physical Sciences-Oncology Center, and one of the study’s senior authors. “Our study looked more closely at the steps that actually initiate metastasis. By doing this, we were able to develop a unique therapeutic that directly targets metastasis, not the growth of the primary tumor.”
This drug cocktail was tested on mice in the lab, but has not yet been tested on humans. Wirtz said the feedback they have gotten from other researchers has been positive and others see “real potential for this approach.”
See the full study in the May 26 online issue of Nature Communications.