Body tissue discovery suggests how cancer might spread

"Scientists have identified a new human organ hiding in plain sight, in a discovery they hope could help them understand the spread of cancer," The Independent reports.

The story is not quite as groundbreaking as it sounds. Researchers have known about the "interstitium" – the tissue between organs and vessels in the body – for a long time. They have also known that fluid is present within this tissue, the research has simply better visualised its structure. An organ is a group of different tissues that work together to carry out a specific function. Whether the interstitium is complex enough to qualify as an organ is debatable.

The current discovery came about when researchers, using a new imaging technique, noticed a net-like structure surrounding fluid-filled spaces in the tissue around the bile duct. They also found similar structures around other tissues and organs.

The fluid within this structure appeared to drain into the lymphatic system – a network of vessels that drains fluid from the body. The researchers found cancer cells in some of this tissue, and suggested that the fluid-filled spaces within the interstitium might be one of the ways cancer cells can spread, and may be how cancer ends up in the lymph nodes.

More research is likely to be needed to find out whether this improved understanding of the interstitium can be used to fight disease.

Where did the story come from?

The study was carried out by researchers from the Icahn School of Medicine at Mount Sinai in New York, as well as other medical schools and universities in the US. It was funded by the National Institutes of Health and the Center for Engineering Mechanobiology in the US. Some of the authors had received sponsorships from or been paid for consultancy by companies producing imaging equipment.

The study was published in the peer-reviewed journal Scientific Reports. It is open access, meaning it can be accessed for free online.

Both the UK and global media have had a field day, with The Sun saying the "organ" hadn't "been noticed until now", despite the fact that the term interstitium has been used to describe this tissue for years.

What kind of research was this?

This mainly laboratory-based research looked at the structure of the tissue in between various organs of the body.

The researchers used a new way of looking at tissues in the body called probe-based confocal laser endomicroscopy (pCLE). This allowed them to look at the structure of tissues while a person was having an endoscopy – the insertion of a tube with a camera into the digestive tract to carry out medical investigations. While looking at the tissues around the bile duct and pancreatic ducts, they noticed a net-like structure surrounding fluid-filled spaces. They didn't know what this structure was, so investigated more closely.

Advances in the technologies researchers can use to look at tissue and organs while a person is still alive have helped them to better understand their 3-dimensional structures, and how they work.

In the past, researchers would only have been able to look at tissues and organs after they were removed from the body. The ways that these tissues and organs had to be treated to preserve and investigate them would affect their structure.

What did the research involve?

The researchers carried out further investigations of the tissue around and in between various organs to understand its structure. The tissue they found is called the "interstitium" (a Latin-based word meaning "the space between") or "interstitial space".

The researchers first used the pCLE technique to look closely at the tissue around the bile duct in 12 patients having surgery to remove tissue from this area. They injected fluorescent dye into the area and took photos of what they saw with pCLE. The tissues were then removed as part of the patient's surgery. The researchers then rapidly froze this tissue and cut thin slices of it to look at its structure under the microscope. They used special stains that stick to different parts of cells and proteins, to help them identify the different parts of the tissue.

They also used these techniques to look at whether similar structures could be seen around and in between other organs and tissues, such as the skin, digestive system, arteries, airways in the lungs, muscles and fatty tissue.

Finally, they examined these structures around the stomach and skin of 5 patients with cancer in these organs. They wanted to see if these spaces might be invaded by the cancerous cells, as they could be a pathway by which cancer could move from one organ to another.

What were the basic results?

The researchers observed a net-like structure surrounding fluid–filled spaces around the bile duct. They found that the "strings" of the net contained collagen, a protein which acts as a kind of scaffolding around the pockets of fluid. These collagen bundles were lined on one side – the side not facing the fluid – with flat cells. They observed similar structures in the tissue surrounding the skin, the digestive tract, bladder, airways and blood vessels.

They also made other observations that suggested the fluid in the interstitial spaces drains into the lymphatic system. The lymphatic system is a network of fine vessels that drains fluid (called lymph) from the various tissues of the body into the blood, taking away waste products and also bacteria and viruses. The lymph contains white blood cells, which help to fight infection.

Cancer can spread through the lymphatic system, so the researchers wanted to see if cancer cells might also spread into the interstitium. Sure enough, they found that in some of the stomach and skin cancer tissue they looked at, cancer cells had spread into the interstitium.

How did the researchers interpret the results?

The researchers' conclusions were that our understanding of the anatomy of the tissue in between the tissues and organs of the body should be revised as "rather than being densely-packed barrier-like walls of collagen, they are fluid-filled interstitial spaces". They suggest that these spaces could be compressed or stretched, and therefore act as "shock absorbers" in the body. It may also play a role in the accumulation of excess fluid in body tissues called "oedema". These open, fluid-filled spaces may also make it easier for cancer cells to spread than if the space was solid.

Conclusion

Researchers have known about the presence of interstitial tissue – connective tissue and fluid between organs in the body – for a long time. This study furthers our understanding of its structure, and suggests it may have roles in the body we did not know about.

In the past, researchers could only look at the detailed structure of tissue after it had been removed from the body. The techniques used in preserving and dissecting the tissue would have forced the fluid out. We know that build-up of fluid in such tissues leads to conditions such as oedema. The difference is that the new techniques can now see details of the fluid-filled collagen pockets rather than what looked like solid collagen bundles. This work has been made possible by advances in the technology we can use to look at tissue while it is still in the body.

While these initial results suggest the fluid-filled spaces might be one of the ways cancer cells can spread, more research is needed to understand the interstitium and its possible role in cancer and other diseases.