Understanding how tumors reprogram their micro-environment in order to survive

May 29, 2018 10:10 am

Ruth Scherz-Shouval, Ph.D.
By David Schiff

It is now well known that in order to proliferate and spread, cancer cells must recruit and reprogram normal cells to support them instead of fighting them. The normal cells are not mutated, so how do the cancer cells hijack them? Could it be that the cancer cells trick the normal cells into reacting as though the body is under some sort of stress so that these normal cells protect the cancer cells instead of killing them?

Ruth Scherz-Shouval, Ph.D., a senior researcher at the Weizmann Institute of Science in Israel, has already shown this happens in the case of a protein called Heat Shock Factor 1 (HSF1). This protein’s job is to protect cells when they are subjected to unusually high temperatures—whether from external sources like a 100°F day or internal sources such as inflammation or fever. Dr. Scherz-Shouval has found that HSF1 is a strong enabler of malignancy when activated in normal cells residing within tumors in patients with lung or breast cancer.

Now, funded in part by a Gesher Award for Excellence in the field of Cancer Research, Dr. Scherz-Shouval and her team are working to understand how cancer cells manage to hijack HSF1 and other stress responses. The award is funded by the Israel Cancer Research Fund in cooperation with the Israel Ministry of Science, Technology and Space.

“A tumor is more than just cancer cells,” explained Dr. Scherz-Shouval. “It’s a microenvironment that includes immune cells that were supposed to kill the cancer cells; but now, for some reason, they don’t do that. They actually help the cancer cells evade the immune system. It also includes connective tissue, blood vessels that feed the tumor oxygen, and growth factors. We think of the microenvironment as the soil in which the cancer cells grow. If we take away the soil, the tumor will die.”

Because normal cells in the tumor microenvironment are not mutated, Dr. Scherz-Shouval said, “It may be easier to target them or even re-educate them, to remind them that they are supposed to be trying to kill the tumor and not to help the tumor survive.”

The research team began by analyzing tissue samples from patients with early stage breast and lung cancer. Using a staining technique that allowed them to identify cells in which HSF1 was activated, they found many more activated cells in the tumor microenvironment than in other tissues.

Next, the researchers found that by removing HSF1 from normal cells in the tumor microenvironment of mice, they could greatly reduce the number of cancer cells. The same held true when they removed HSF1 from tumor microenvironments in laboratory dishes. Working in dishes outside the body is allowing the scientists to test different chemical molecules to try to find something that can later be translated into a drug that can kill cancer cells by eliminating HSF1 in the tumor microenvironment.

In addition to developing treatment drugs, increased understanding of how cancer cells use HSF1 and other stress response factors has the potential to help with prognosis. If an early-stage tumor has few HSF1 positive cells, doctors may be able to choose to monitor the tumor while treating it less aggressively, sparing patients the suffering associated with more aggressive treatments.



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