Institute of Science and Technology (IST) Austria scientists have just discovered mechanisms that help human immune cells invade tumor tissues.

Knowing the exact time when immune cells will attempt to invade tumors can be difficult to identify. For researchers to study the cell invasion process thoroughly, Professor Daria Siekhaus and her colleagues, needed something more reliable. It is why they used fruit fly embryos for the study.

During the development of the fruit fly embryos, macrophages, a known dominant type of immune cells, journeys from the spot where they are created to where they will be needed by invading tissues. Macrophages do this at a certain time point, allowing scientists to analyze the process within the tiny transparent animals. With assistance from the state-of-the-art Bioimaging Facility at IST Austria, the team watched as the macrophages - that were marked with special green fluorescent protein dyes - make their way into the invading tissues.

Armor Creation

Fly
(Photo : Thierry Fillieul from Pexels)

It is largely unknown which cellular changes are necessary for the phenomenon and which specific genes trigger the alterations. With the team's new study published in the journal PLOS Biology, titled "Fos regulates macrophage infiltration against surrounding tissue resistance by a cortical actin-based mechanism in Drosophila," scientists shed light on the mechanisms at play that is essential in both health and disease. Siekhaus explains that the team previously found a specific gene known as Dfos enhanced in the immune cells. However, the scientists were wondering what the gene did.

She adds that they can now prove that the gene triggers the assembly of actin filaments. These threads of protein are concentrated inside the macrophage's cell membrane, or the cell cortex, which gives the surface of the cell stability.

The team shows that through a complex cascade involving various proteins, actin filaments become denser and more interconnected, forming a stable shell. Siekhaus says that the team hypothesizes that the mechanism works similarly to tanks, in the way that it deforms the surrounding cells while at the same time protecting and shielding the immune cell's nucleus from pressures as it invades tissues.

Additionally, Siekhaus' team was able to show in vivo that the lack of actin shells make it significantly harder for immune cells to successfully infiltrate unless the tissues have been made softer.

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Fighting Cancer and Strengthened Immune Cells

Although fruit flies are significantly different from vertebrates like mice and humans, there are many similarities in their gene function. Together with Medical University of Vienna Professor Maria Sibilia, researchers found evidence that the vertebrates Fos gene, equivalents to Dfos in fruit flies, activates the same genetic pathways. Siekhaus explains that they believe that the same mechanisms found to be in play in fruit flies also played a significant role in vertebrates, reports EurekAlert.

This discovery raises hopes that the team's findings could help identify new targeted treatments for cancer. In the field of immuno-oncology, scientists are looking for new ways to activate the human body's immune system to target and attack tumors. 

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