Discovery May Offer Insight in Cancer Treatment

It’s sticky and has a name that would be right at home in the dietary supplement aisle at the grocery store. But fibronectin, produced by a kind of cellular machinery recently discovered by researchers at the National Institute of Dental and Craniofacial Research (NIDCR), might possibly provide insights into protective organ barriers and how they may be infiltrated by cancer later in life.

The investigation was initiated after graduate student Jiaoyang Lu, PhD, stumbled onto a discovery as he was studying cancer cells under a microscope. He noticed that when the cells were placed on basement membranes or extracted components of them, vast numbers of fibronectin fibers began to accumulate. This was in stark contrast to the sparser gatherings that occurred when cancer cells or other kinds of cells were placed on connective tissue.

The study, headed by Kenneth Yamada, MD, PhD, and published online in Developmental Cell, examined the sheet-like basement membranes, or membranous linings that encase our organs and tissues, maintaining their integrity, while keeping harmful substances—such as cancer cells—out.

Fibronectin, a thread-like protein distributed in bundles, has long been known to cover the surface of basement membranes. Its stickiness allows cell adhesion and migration along the substrate. But until now, the functions of these substances and their genesis were not understood.

TINY ASSEMBLY LINE

Using high-resolution microscopy and fluorescent labeling to capture action, the NIDCR investigators found that through contraction-like movements, the cells lay fibronectin down on the membrane surfaces, as if paving a driveway. And while the cells form focal adhesions as expected, the surprising thing is that instead of remaining in place, many of these adhesions slide inward toward the center of the cell, leaving a trail of fibronectin fibers in their wake. So, the focal adhesions were not only mobilizing the cells, but also assembling the fibronectin fibers.

According to the researchers, the mechanics of this process appear to involve wire-like cell skeleton parts called actin cables, which extend out in straight lines throughout the cell. These give it structure and expedite travel to various areas in the cell in conveyer belt style.

The contractions that were observed were the result of the shortening of these cables, which reel in focal adhesions. The movement results in fibronectin being stretched to expose secondary attachment sites. Continued movement creates more attachment sites until a sort of trail is formed, as cells migrate across basement membranes in search of their final destination.

THIS COULD EXPLAIN A LOT

Yamada believes that this revelation sheds light on how fibronectin deposits along basement membranes form. It may even give us an idea of how organs, such as salivary glands, form during development and how they’re sometimes infiltrated by cancer in adulthood.

Yamada thinks it’s possible that fibronectin deposits are involved in embryonic development. But researchers also believe that fibronectin’s sticky properties provide an attachable surface for cancer cells in adults, facilitating invasion into tissues.

In fact, Yamada’s team reports confirmation that fibronectin promotes the invasion of oral cancer cells across basement membrane barriers. Such findings could explain how cancer becomes invasive and point the way toward way toward new treatments. Research is ongoing.