Building Better Mouse May Lead to Better Mesothelioma Mousetrap

The goal of mesothelioma research is to build a better mousetrap for getting rid of this vicious cancer. One group of mesothelioma researchers has been focused instead on building a better mouse.

Mice play a very important role in mesothelioma research. Scientists use the furry rodents to test theories about how mesothelioma develops and about how to stop it.

Mice are favored for this purpose because aspects of their anatomy and biologic processes mirror those of humans.

To study the effect of mesothelioma on mice the researchers “infect” them with either asbestos fibers or actual mesothelioma cells. Then, they observe what happens afterward. Or they can try out novel drug therapies and see how things turn out.

A Problem with Mice in Mesothelioma Studies

But there’s a problem with this approach. Researchers can’t observe what happens if the mice have compromised immune systems.

The solution is obvious. Just use mice that don’t have compromised immune systems. Easier said than done.

That’s because getting mesothelioma to quickly spark and then mushroom within a mouse’s body normally causes a loss of the immune system’s integrity.

Researchers from several hospitals and universities in Italy and Holland have been working together to induce mesothelioma in mice while avoiding the problem of compromised immune systems.

The solution they came up with involves injecting the mice with murine mesothelioma cell lines AB1, AB12 and AB22. It turns out that these three cell lines grow rapidly in mice that have healthy immune systems.

Because of this, the researchers discovered they could examine biomarker configurations within those particular mesothelioma cells.

Studying HMGB1 Contribution to Spread of Mesothelioma

In turn, that allowed them to examine the cells’ response to damage-associated molecular pattern HMGB1. HMGB1 stands for High Mobility Group Box 1 protein.

Writing in the journal Scientific Reports, the researchers explained that HMGB1 contributes to the spread of mesothelioma.

Take HMGB1 away and immunogenic cell death can occur. That fact alone makes HMGB1 worth studying, they insisted.

“HMGB1 is passively released by primary human mesothelial cells exposed to asbestos, recruits macrophages and thus contributes to the initial stages of inflammation, inducing the secretion of TNF-α and other cytokines,” the researchers wrote.

“When mesothelial cells become transformed in an HMGB1-rich environment, most of the resulting malignant mesothelioma cells require HMGB1 to grow and to invade nearby tissues,” they added.

Thus, suppressing HMGB1 may have therapeutic value. But it can’t be known for sure whether it does or doesn’t have therapeutic value without testing it in mice that have intact immune systems, the researchers explained.

And that’s where the new “mouse model” the researchers developed will ultimately pay off, they indicated.

The title of the researchers’ study is “Human Malignant Mesothelioma is Recapitulated in Immunocompetent BALB/C Mice Injected with Murine AB Cells.”

The researchers are mostly from institutions based in Milan, Italy. These include Milano Bicocca University, San Raffaele Vita-Salute University, Fondazione Filarete, Università degli Studi and Mario Negri Institute.

Others on the team hailed from the University of Eastern Piedmont in Novara, Italy, Maggiore Della Carità Hospital in Novara, Italy, and Netherlands Cancer Institute in Amsterdam.