A study conducted by Johns Hopkins researchers and collaborators has found a biochemical signaling process responsible for causing condensed cancer cells to separate from a malignant tumor and spread the disease to somewhere else in the body. In the study, the researchers utilized two existing drugs in combination to alter this process and in turn slow cancer’s inclination to travel, a behavior known as metastasis.
Metastasis is associated to 90 percent of cancer deaths and anything that is capable of derailing this action could potentially improve cancer patients’ prognosis. When the researchers closely examined cellular events that are responsible for promoting metastasis, they discovered the vital, new signaling process.
“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 lead author Hasini Jayatilaka, a postdoctoral fellow at John Hopkins’ Physical Sciences-Oncology Center. “At a fundamental level, we found that cell density is very important in triggering metastasis. It’s like waiting for a table in a severely overcrowded restaurant and then getting a message that says you need to take your appetite elsewhere.”
By utilizing a medication mix, the researchers were able to prevent this microscopic message from getting delivered. The researchers warned that this treatment had not yet been tested on humans with cancer, but was tested in animal models. However, the finding provides to an encouraging new focus for cancer research – impeding the biochemical activity that is responsible for prodding cancer cells to spread elsewhere in the body.
A senior author of the study, Denis Writz, director of Johns Hopkins’ Physical Science-Oncology Center, said there are currently no commercial drugs being produced specifically to stop metastasis, because pharmaceutical companies think the optimal strategy to prevent metastasis is to annihilate the primary tumor from which the cancer originates.
Two pivotal drivers of metastasis are the cancer cells’ ability to travel through surrounding tissue until they finally get to the bloodstream and their likelihood to reproduce a rapid rate. In the bloodstream, the cancer cells can get a free ride to spread cancer throughout the body.
The researchers utilized a 3D environment that replicates human tissue to determine how these activities begin. They found that as two forms of cancer cells reproduced and produced more dense conditions in the test site, these cells released specific proteins that motivated migration. These proteins were identified as Interleukin 8 (IL-8) and Interleukin 6 (IL-6).
“IL-6 and IL-8 seem to deliver a message to cancer cells, telling them to move away from the densely populated primary tumor,” said Jayatilaka.
In their animal studies, the research team discovered that implementing two existing drugs, Reparaxin and Tocilizumab, prevented the receptors responsible for enabling cancer cells to receive their relocation orders. The FDA approved Tocilizumab for the treatment of rheumatoid arthritis and is currently in trials for use in ovarian cancer cases. Other researchers are evaluating Reparaxin as a potential treatment for breast cancer.
The study was published online in Nature Communications on May 26, 2017.