Newly Discovered ‘Organ’ May Help Explain How Cancer Spreads

A newfound organ, the interstitium, is seen here beneath the top layer of skin, but is also in tissue layers lining the gut, lungs, blood vessels, and muscles. The organ is a body-wide network of interconnected, fluid-filled compartments supported by a meshwork of strong, flexible proteins. (Illustration by Jill Gregory. Printed with permission from Mount Sinai Health System)

(CN) – Layers within the human body previously believed to be dense, connective tissues have now been identified as an organ, according to a new study that could help scientists understand the spread of cancer within the body.

In the report, published Tuesday in the journal Scientific Reports, a team of researchers provides an updated description of the interstitium, which is actually comprised of interconnected, fluid-filled compartments that are supported by a meshwork of flexible and strong connective tissue proteins.

The compartments may serve as shock absorbers that protect tissues from tearing as vessels, muscles and organs squeeze, pulse and pump. The finding could also explain why cancer that invades the interstitium becomes much more likely to spread, according to the report.

The network of fluid-filled compartments drains into the lymphatic system and is the source of lymph, the fluid critical to the functioning of immune cells that generate inflammation. Additionally, the cells in the interstitium, and the collagen bundles they line, adjust with age and may contribute to the stiffening of limbs, the wrinkling of skin and the progression of sclerotic, fibrotic and inflammatory diseases.

Scientists have long known that more than half the fluid in the body is found within cells. Roughly one-seventh of bodily fluids is inside the heart, lymph nodes, lymph vessels and blood vessels. The remaining fluid is “interstitial,” and the new report is the first to define the interstitium as an organ – one of the largest of the body, according to the team.

The researchers say the fluid-filled compartments have been overlooked due to the medical field’s dependence on the examination of fixed tissue on microscope slides, which are believed to offer the most accurate glimpse of biological reality. Scientists prepare tissue for examination on microscope slides by treating it with chemicals, cutting it thinly, and dyeing it to highlight crucial features. The team found that the removal of fluid as slides are created causes the connective protein meshwork surrounding the once-filled compartments to pancake, like a crushed soda can.

“This fixation artifact of collapse has made a fluid-filled tissue type throughout the body appear solid in biopsy slides for decades, and our results correct for this to expand the anatomy of most tissues,” said co-senior author Neil Theise, a professor at New York University School of Medicine.

“This finding has potential to drive dramatic advances in medicine, including the possibility that the direct sampling of interstitial fluid may become a powerful diagnostic tool.”

The findings are based on a newer technology known as probe-based confocal laser endomicroscopy, which combines the slim, camera-carrying probe traditionally snaked down a patient’s throat to view the insides of organs with a laser which illuminates tissues and sensors that analyze the reflected patterns. It provides a microscopic view of living tissues, rather than fixed ones.

Using this technology, endoscopists and report co-authors David Carr-Locke and Petros Benias witnessed something odd while probing a patient’s bile duct for cancer spread: a sequence of interconnected cavities in this submucosal tissue level that did not match any known anatomy.

This surprising discovery led Carr-Locke and Benias to walk the images into the office of their partnering pathologist, Theise. Curiously, when Theise created biopsy slides out of the same tissue, the reticular pattern disappeared. They would later verify that very thin spaces observed in biopsy slides, typically dismissed as tears in the tissue, were instead the remains of collapsed, previously fluid-filled compartments.

For the study, the team gathered tissue specimens of bile ducts during 12 cancer surgeries that were involved removing the bile duct and the pancreas. Moments before blood flow to the target tissue was clamped off, patients underwent confocal microscopy for live tissue imaging.

Once the researchers identified this new space in images of bile ducts, they soon recognized it throughout the body wherever tissues were compressed or moved by force. The cells lining the space are also atypical, potentially responsible for creating the supporting collagen bundles around them, according to the team.

Theise says the cells may also be mesenchymal stem cells, which are known to be capable of contributing to the formation of scar tissue observed in inflammatory diseases.

The protein bundles seen in the space probably generate an electrical current as they bend with the movements of muscles and organ, and may be affected by techniques like acupuncture, Theise says.

The research was funded partially by a grant from the National Institutes of Health.

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