Defects in tissue trigger disease-like transformation of cells

One small defect in tissue boundaries known as the basement membrane can lead normal cells to take on characteristics of diseased cells, such as cancer cells, and invade the surrounding tissue.

Defects in tissue trigger disease-like transformation of cells
Image: Washington University in St. Louis

A small termite can lead to big problems. They are very good at chewing the wood. Termites can do even more damage if the wood is already broken or has another defect.

A new study by the Mechanical engineers at Washington University in St. Louis discovered the same impact in a portion of the body’s tissue: One little defect in tissue limits known as the basement membrane can lead typical cells to go up against qualities of diseased cells, for example, cancer cells, and attack the surrounding tissue.

Scientists discovered this feedback loop with epithelial cells. These simple cell colonies act as the body’s defense system against the outside world and also line the inside of the throat, intestines, blood vessels and organs, meaning the epithelial cells could provide a little link to a much bigger issue.

Identifying this association could help scientists to find potential new therapies to halt cancer metastasis.

In cancer, epithelial cells transition into mesenchymal types that can degrade the basement membrane. This process is originally stimulated by enzymes called matrix metalloproteinases (MMPs) that leads to further defects in healthy tissue and allows cancer to metastasize.

This is the first study that reveals the reverse also is true — pre-existing defects in the basement membrane, such as a wound or small incision, are enough to encourage the normal cells to take on disease characteristics, leading to further degradation of the basement membrane.

Scientists manufactured a basement membrane model using a hydrogel-coated with collagen IV, a protein that is the main and most important structural component of the basement membrane. They added normal epithelial cells, which like to stick together, then made a small cut in the gel. After six days, the cells started to break apart, move around and invade the gel, mimicking a tumor invading healthy tissue.

Amit Pathak, associate professor of mechanical engineering in the School of Engineering & Applied Science said, “Because of the defect, the cells started to show signatures of diseased cells. If there was no defect, they would have stayed the same. This small defect of less than one-tenth of a millimeter caused this whole process of these cells changing.”

In order to show that the cells would have remained the same without the defect, scientists treated them with an inhibitor of MMPs, which are known to degrade the basement membrane in wound healing. The cells did not change and did not invade the basement membrane.

Pathak said, “This finding shows that we shouldn’t take basement membrane degradation as an inevitable outcome. In addition to targeting tumor cells, we can determine therapeutic strategies that make the basement membrane more stable. If it is more stable, then we can at least slow down and possibly reverse metastasis.”

The research is published online May 16 in Integrative Biology.