Mayo Clinic Cancer Center leads the field in researching the impact and effect of SULF1, a protein whose normal role is to degrade heparin sulfate proteoglycans -- molecules that are part sugar and part protein. Mayo scientists have found that the protein also helps inhibit tumor growth. Now, Mayo researchers are studying a related gene, SULF2.
The role of the SULF2 gene and protein has not been fully defined, but in this study, researchers investigated the effect of SULF2 on liver tumor growth in the laboratory. They found that increased expression of SULF2 enhances cancer cell growth and migration, whereas decreased expression reduces both.
“The liver is designed to excrete toxins, and its tumors are no exception,” says Mayo Clinic gastroenterologist Lewis Roberts, M.B.Ch.B., Ph.D., the study’s primary investigator. “Our problem is that the tumors tend to excrete chemotherapeutic agents rather than be affected by them. So we are looking for ways to get around that.”
The researchers sought answers by examining a protein related to one they already knew had a role in suppressing liver tumors. SULF1 and SULF2 are similar proteins, but cause opposing results. SULF1 removes sulfate groups that allow growth factors to bind to cells, thus inhibiting growth. The investigators found that SULF2 did the opposite -- it increased binding of a specific growth factor, fibroblast growth factor 2 (FGF2), to tumor cells, and also increased expression of the heparan sulfate proteoglycan glypican 3 (GPC3), which plays an important role in cell division and growth. These findings were confirmed in mouse models.
This discovery indicates if scientists can decrease the levels or activity of SULF2 in a tumor, they might be able to stop its development. Mayo researchers are exploring use of an agent that mimics heparin and inhibits SULF2. They are also examining whether preventing heparin sulfate synthesis would inhibit tumor growth.
“If something has a very broad effect on signaling by growth factors, it may lead to an effective treatment,” says Jinping Lai, M.D., Ph.D., a Mayo oncology researcher and the lead author of the study. “SULF2 has a number of characteristics that make it an attractive target, such as the fact that it is widely present in tumors. We are exploring a number of options with SULF2 as a focal point for treatment not only in liver cancer, but also in head and neck, pancreas, breast and other types of cancer.”
The researchers hope to identify drugs that block SULF2, and seek to thoroughly understand the mechanisms involved, including the determination of what other growth signaling pathways are affected by SULF2. They are also looking further at GPC3 as a potential biomarker for liver cancer or as a possible therapeutic target.
In 2007, Dr. Lai presented information at the annual meeting of the American Association for Cancer Research on the role of SULF2 in survival of patients with head and neck cancer -- the first concrete link to survival of patients with a specific tumor type.
Elizabeth Zimmermann | EurekAlert!
Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory
How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
24.03.2017 | Materials Sciences
24.03.2017 | Physics and Astronomy
24.03.2017 | Physics and Astronomy