Israeli Researchers Say Anti-inflammatory Drugs Could Slow Progress of Breast Cancer

Scientists from Tel Aviv University discover how breast cancer cells hijack the body's natural mechanisms for repairing damaged tissue

Ido Efrati
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Breast cancer cells (in red) that have metastasized into the lungs.
Breast cancer cells (in red) that have metastasized into the lungs.Credit: Dr. Noam Cohen
Ido Efrati

Tel Aviv University researchers have discovered how breast cancer cells hijack the body’s natural mechanisms for repairing damaged tissue to instead help tumors grow and metastasize to the lungs.

In the study, published three months ago in the journal Nature Communications, the researchers demonstrate how cancer cells use the body’s natural inflammatory pathways, and argue that using anti-inflammatory drugs to deal with chronic inflammation could slow progress of the disease.

“Cancer is a stealthy enemy which succeeds in deceiving the body’s systems and enlisting them for its needs,” says Prof. Neta Erez, head of the pathology department at the university’s Sackler Faculty of Medicine, who directed the study. “We focused on the tissue-connecting cells called fibroblasts. When things are normal, the fibroblasts play a central role in healing damaged and wounded tissue. But studies from recent years show that they are also connected to inflammatory, cancer-supporting processes. We sought to find the mechanism and figure out how fibroblasts are enlisted to assist cancer.”

Fibroblasts rest in the tissues. When they identify damage, they secrete certain chemicals that summon immune system cells to help. As part of this process, the fibroblasts make blood vessels more permeable to allow the immunity cells to penetrate the tissue and do their job. This is the body’s natural inflammatory pathway in cases of tissue damage.

Researchers Prof. Neta Erez (left) and Dr. Nour Ershaid of Tel Aviv University.
Researchers Prof. Neta Erez (left) and Dr. Nour Ershaid of Tel Aviv University.Credit: Robert Hoffman

Researchers Dr. Nour Ershaid and Dr. Yoray Sharon obtained female mice fibroblasts of three types; without cancer, with an early stage breast tumor and with an advanced tumor that had already metastasized to the lungs. They then examined the various proteins in these tissues. Later, they also analyzed a publicly available set of tumor samples from 53 women and the fibroblasts of 79 breast cancer patients.

“In the fibroblasts taken from the diseased mice, and from the nearly 80 women with breast cancer, we found to our surprise an overexpression of proteins indicating an inflammatory pathway called inflammasome,” Erez explains. “This is a familiar pathway of the immune system that allows it to identify tissue damage and summon additional immunity cells to create an inflammation that will fight the damage. Until now the inflammasome pathway had never been seen in cancer-associated fibroblasts.”

The researchers sought to examine how the inflammation process contributes to the and if this was indeed some kind of mechanism in which a tumor deceives normal cells and enlists them to its benefit. To examine this, they again used mice with breast cancer, and through genetic engineering blocked the production of the inflammatory pathway proteins in the cancer-associated fibroblasts. They found that blocking the proteins delayed the development of the tumor, and in the cases of metastatic cancer the number of secondary growths was reduced. The researchers thus concluded that the inflammation mechanism was being hijacked to help the cancer develop.

“One can describe cancer as a wound that will never heal, a regular and continuous process of tissue damage,” says Erez. “One of the ramifications is the body’s inflammatory response, which identifies the cancer as a wound to the tissue, similar to any other blow that can be fixed. As such, it sends a large number of immunity cells and launches the repair mechanisms that encourage the growth of blood vessels. The cancer makes use of all of these, meaning that the immune system is effectively helping the cancer develop.”

A doctor examines breast cancer cells at Beilinson Hospital in Petah Tikva.
A doctor examines breast cancer cells at Beilinson Hospital in Petah Tikva.Credit: Alon Ron

Given this discovery, the researchers suggest using anti-inflammatory drugs, which suppress the secretion of the chemicals that the fibroblasts secrete to summon the immune system cells. “Such treatment could be given to women after surgery to remove a breast tumor, with the goal of preventing further metastasis. We believe that this method could also be appropriate for other types of cancerous tumors,” Erez says.

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