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Celebrating hyaluronan research – new treatment can improve cancer prognosis

Professors Raija and Markku Tammi have conducted pioneering hyaluronan research for an impressive 35 years. They were the first in the world to demonstrate the role of hyaluronan in cancer prognosis and skin function, among other things. The Hyaluronan Symposium to be held in Kuopio on 10 November will cover the latest developments in hyaluronan research, presented by Kuopio-based researchers and the field’s top international scholars alike.

Hyaluronan is one of the key macromolecules in the extracellular matrix. It supports normal cell mobility and proliferation, while also playing a role in tumour growth and tumour spreading. At the turn of the millennium, the research group of Raija and Markku Tammi was the first in the world to show that in many cancers, the more there is hyaluronan around the tumour, the worse the prognosis.

“In breast cancer, for example, the survival rate is as low as 20 per cent, if hyaluronan is abundantly present. With little or no hyaluronan present at all, the survival rate is over 90 per cent,” Markku Tammi explains.

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Image of live human breast cancer cells that generate a thick layer of hyaluronan around them.  Hyaluronan is seen in red in the image.

Later on, the group working at the Kuopio Campus has also shown that hyaluronan can promote the spreading of cancer by forming protrusions on the cancer cell surface. Vesicles released from these protrusions transport cellular matter to the vicinity of the tumour and also elsewhere in the body.

The group’s findings have led to the development of a novel cancer drug. Developed by the American biopharmaceutical company Halozyme Therapeutics, the drug is based on an enzyme that breaks down hyaluronan. Currently in stage two clinical trials, the treatment results have been promising. By reducing the amount of hyaluronan that protects the tumour, cancer treatments can be more effective.

“The efficacy of the new drug has first been studied in pancreatic cancer, which is associated with particularly high hyaluronan levels and patient mortality. The drug has helped double patients’ life expectancy, although in the case of pancreatic cancer, we are often talking about a couple of months only.”

The same drug could also prove beneficial in the treatment of ovarian, gastric and colon cancer, for example.

The research group also has a long history of research into skin biology, and they have made pioneering observations of the role of hyaluronan in skin function, for example as a regulator of epithelial growth and differentiation.

The group’s more recent research has shed new light on factors that cause an increase in the amount of hyaluronan. Hyaluronan is a glucose-derived polymer the production of which requires cellular UDP-sugars as building blocks.

“By limiting the availability of these building blocks, we could inhibit hyaluronan formation. This would provide another way of influencing the amount of hyaluronan,” Markku Tammi says.

The group’s observations are interesting also from the viewpoint of inflammatory diseases. Irregular hyaluronan metabolism is known to promote the inflammatory state in, for example, asthma, rheumatism and chronic wounds, as well as in low-grade inflammation associated with diabetes and arterial diseases.

“We’ve recently learned about interesting results by other scientists relating to, for example, animal models of type 1 diabetes.  In a study by Stanford University, limiting the production of hyaluronan stopped an autoimmune reaction and the development of diabetes.”

“Hyaluronan-coated drug transporters are also a hot topic of research globally. Malignant tumours have plenty of hyaluronan receptors at which these transporters could be targeted, allowing for the cancer drug to become concentrated in the tumour.”

Hyaluronan can bind large amounts of water, which is why it is injected into the joints of osteoarthritis patients to serve as a lubricant, and used in cosmetic treatments as a filler under the skin.

“Hyaluronan used in injections is in an inactive form and it is considered safe. However, there is some controversy over its benefits in the treatment of osteoarthritis,” Raija Tammi says.

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Raija and Markku Tammi recently received the Rooster Prize of the International Society for Hyaluronan Sciences in recognition of their achievements in hyaluronan research.  Traditionally, hyaluronan for medical purposes has been isolated from rooster combs.

Pioneers in a growing university

The work of Raija and Markku Tammi in hyaluronan research will be celebrated in the Hyaluronan Symposium on 10 November. The symposium will showcase latest achievements in hyaluronan research made in Kuopio and elsewhere in the world. In addition to viewpoints relating to cancer and inflammation, the role of hyaluronan in infarction recovery and the regulatory mechanisms of hyaluronan synthesis will also be addressed in the symposium.

“It is important for young researchers to form contacts with the field’s leading international scholars. Hyaluronan research will continue here in Kuopio, although we will gradually step aside,” Raija Tammi says.

Both of them have reached their retirement age this year, Raija Tammi after having served at the university as Professor of Anatomy (Cellular Biology), and Markku Tammi as Professor of Anatomy.

“There is more to life than just research.”

Raija and Markku Tammi trained to become physicians and obtained their MD degrees at the University of Turku. In 1979, they began teaching and studying anatomy in what was known as the University of Kuopio at the time, still operating in temporary facilities on Puistokatu, in the former garrison.

“We had to set up everything ourselves, starting from the laboratories. But this was also an advantage, as we got to do pioneering work in a growing university,” Markku Tammi says.

They further refined their skills in the US, where both ended up spending several years as researchers. Among their most important achievements in methodological development is a unique probe that locates hyaluronan in tissue.

Markku Tammi looks back on the early years, remembering how lectures were held in changing locations in the city, with changing degrees of comfort.

“In winters, I remember students taking notes with their coats and mittens on.”

The university has come a long way since. Today, the facilities of the Institute of Biomedicine are comfortable, with state-of-the-art learning environments and virtual models for the study of anatomy.

“The development of digital methods has opened up great avenues for teaching. Here in Kuopio, all medical students still participate in a real dissection, which continues to be a sound method for learning about anatomy,” Raija Tammi concludes.

Hyaluronan Symposium 10.11. 2017 in Kuopio

http://www.uef.fi/documents/10184/1670068/image_0072-600x300.jpg/dd22aed7-4b71-402c-b01a-fb8da71a2c39?t=1510126351000

Image of a human connective tissue cell that produces cable-like hyaluronan chains around it. These are shown in blue in the image.
Text  Ulla Kaltiala Photos Kirsi Rilla and Raija Törrönen