How metastases develop in the liver

Inflammation in tissue creates a niche for tumor cells

2014-10-14

(Press-News.org) This news release is available in German.

In order to invade healthy tissue, tumor cells must leave the actual tumor and enter the bloodstream or lymphatic system. For this purpose, they use certain enzymes, proteases that break down the tissue surrounding the tumor, thus opening the way for tumor cells to reach blood or lymphatic vessels. To keep the proteases in check, the body produces inhibitors such as the protein TIMP-1, which thwart the proteases in their work.

But during development of metastases, the control function of this inhibitor appears not only to fail but to swing in the opposite direction and to actually promote the formation of metastases. Observations in numerous cancer patients have shown that high levels of the inhibitor TIMP-1 in the blood did not slow the spread of cancer. On the contrary, it actually hastened the progression of the disease. The research group led by Prof. Achim Krüger at the Institute for Molecular Immunology and Experimental Oncology of Klinikum rechts der Isar has now been able to explain this contradiction experimentally, thus shedding light on a mechanism that leads to the formation of metastases in the liver.

Niche for cancer cells

Together with his team, he discovered that a high concentration of the inhibitor TIMP-1 induces local inflammation in liver tissue. In response, immune cells known as neutrophils migrate into the organ. Tumor cells circulating through the body in the bloodstream then take advantage of these cellular and molecular changes to lodge in the liver and form metastases. "TIMP-1 creates a zone in liver tissue in which favorable conditions for cancer cells prevail – a fatal development for the very early spread of the primary tumor," Krüger explains.

After the scientists discovered this metastasis-promoting effect of TIMP-1, they succeeded in elucidating the mechanism further and even preventing it. Using an animal model, they found that TIMP-1 recruits immune cells by increasing the levels of a specific signaling molecule in the liver. This signaling molecule binds to a receptor, creating ideal conditions for cancer cells. Using pharmacological substances and antibodies, the researchers were able to block this interaction between the signaling molecule and its receptor, thus inhibiting the metastatic process experimentally.

Kruger summarizes the research results as follows: "The early metastasis of tumor cells usually constitutes the critical step in cancer development. If we can prevent the formation of metastases in the liver, at least in an animal model, that is a major step towards developing new treatments for cancer patients."

INFORMATION: Original publication Seubert B., Grünwald B., Kobuch J., Cui H., Schelter F., Schaten S., Siveke J. T., Ngee H. Lim N. H., Nagase4, Simonavicius N., Heikenwälder M., Reinheckel T., Sleeman J. P., Janssen K.-P., Knolle P. A., and Krüger A., TIMP-1 creates a pre-metastatic niche in the liver through SDF-1/CXCR4-dependent neutrophil recruitment in mice, Hepatology, 2014.
DOI: 10.1002/hep.27378

Contact Prof. Dr. Achim Krüger
Klinikum rechts der Isar of Technische Universität München
Institute for Molecular Immunology and Experimental Oncology
Tel.: +49 89 4140-4463
achim.krueger@lrz.tu-muenchen.de
http://www.imi.med.tum.de

ELSE PRESS RELEASES FROM THIS DATE:

Size of minority population impacts states' prison rates, Baker Institute researcher finds

2014-10-14

HOUSTON – (Oct. 13, 2014) – New research from Rice University's Baker Institute for Public Policy found that states with a large minority population tend to incarcerate more people. According to lead author Katharine Neill, states with large African-American populations are more likely to have harsher incarceration practices, worse conditions of confinement and tougher policies toward juveniles compared with other states. She said these findings provide some support for long-standing arguments among sociology and criminal justice experts that the criminal ...

Uncertain reward more motivating than sure thing, study finds

2014-10-14

Recently, uncertainty has been getting a bad rap. Hundreds of articles have been printed over the last few years about how uncertainty brings negative effects to the markets and creates a drag on the economy at large. But a new study appearing in the February 2015 edition of the Journal of Consumer Research finds that uncertainty can be motivating. In "The Motivating-Uncertainty Effect: Uncertainty Increases Resource Investment in the Process of Reward Pursuit," Professors Ayelet Fishbach and Christopher K. Hsee of the University of Chicago Booth School of Business and ...

Inside the Milky Way

2014-10-14

Is matter falling into the massive black hole at the center of the Milky Way or being ejected from it? No one knows for sure, but a UC Santa Barbara astrophysicist is searching for an answer. Carl Gwinn, a professor in UCSB's Department of Physics, and colleagues have analyzed images collected by the Russian spacecraft RadioAstron. Their findings appear in the current issue of The Astrophysical Journal Letters. RadioAstron was launched into orbit from Baikonur, Kazakhstan, in July 2011 with several missions, one of which was to investigate the scattering of pulsars ...

PTPRZ-MET fusion protein: A new target for personalized brain cancer treatment

2014-10-14

Researchers at the University of California, San Diego School of Medicine have identified a new fusion protein found in approximately 15 percent of secondary glioblastomas or brain tumors. The finding offers new insights into the cause of this cancer and provides a therapeutic target for personalized oncologic care. The findings were published this month in the online edition of Genome Research. Glioblastoma is the most common and deadliest form of brain cancer. The majority of these tumors – known as primary glioblastomas – occur in the elderly without evidence ...

Researchers say academia can learn from Hollywood

2014-10-14

HOUSTON, Oct. 13, 2014 – According to a pair of University of Houston (UH) professors and their Italian colleague, while science is increasingly moving in the direction of teamwork and interdisciplinary research, changes need to be made in academia to allow for a more collaborative model to flourish. Professors Ioannis T. Pavlidis and Ioanna Semendeferi from UH and Alexander M. Petersen from the IMT Lucca Institute for Advanced Studies in Italy published a commentary in the October 2014 issue of Nature Physics, articulating policies that will harmonize academic ...

University of Tennessee study finds crocodiles are sophisticated hunters

2014-10-14

Recent studies have found that crocodiles and their relatives are highly intelligent animals capable of sophisticated behavior such as advanced parental care, complex communication and use of tools for hunting. New University of Tennessee, Knoxville, research published in the journal Ethology Ecology and Evolution shows just how sophisticated their hunting techniques can be. Vladimir Dinets, a research assistant professor in UT's Department of Psychology, has found that crocodiles work as a team to hunt their prey. His research tapped into the power of social media ...

Out-of-step cells spur muscle fibrosis in Duchenne muscular dystrophy patients

2014-10-14

AUDIO: A study in The Journal of Cell Biology suggests that asynchronous regeneration of cells within muscle tissue leads to the development of fibrosis in patients with Duchenne muscular dystrophy. Listen... Click here for more information. Like a marching band falling out of step, muscle cells fail to perform in unison in patients with Duchenne muscular dystrophy. A new study in The Journal of Cell Biology reveals how this breakdown leads to the proliferation of stiff fibrotic ...

University of Calgary research leads to brain cancer clinical trial

2014-10-14

Researchers at the University of Calgary's Hotchkiss Brain Institute (HBI) and Southern Alberta Cancer Research Institute (SACRI) have made a discovery that could prolong the life of people living with glioblastoma – the most aggressive type of brain cancer. Samuel Weiss, PhD, Professor and Director of the HBI, and Research Assistant Professor Artee Luchman, PhD, and colleagues, published their work today in Clinical Cancer Research, which is leading researchers to start a human phase I/II clinical trial as early as Spring 2015. Researchers used tumour cells derived ...

Thyroid carcinoma: Biomarker reveals cancer cause

2014-10-14

CLIP2 serves as a radiation marker: After exposure to radiation from radioiodine, both the genetic activity and the protein expression are increased, as the scientists' studies were able to substantiate. CLIP2 appears to be particularly significant in the development of tumours in the thyroid gland after radiation exposure. The team around Martin Selmansberger, Dr. Julia Heß, Dr. Kristian Unger and Prof. Dr. Horst Zitzelsberger from the Radiation Cytogenetics Research Unit at the Helmholtz Zentrum München discovered a connection between high CLIP2 levels and ...

CWRU studies how women in recovery manage personal networks with family and friend users

2014-10-14

Substance abuse counselors and social workers often recommend recovering addicts establish new networks of non-using friends and supporters. But researchers at Case Western Reserve University's social work school found, for many women in poverty, it's not so easy to drop the users in their lives. Many are people that women depend on for childcare, transportation and other necessities to live. "People in the women's networks might be family members, parents or children, who also use drugs. It's hard to cut these people out of their lives," said Elizabeth M. Tracy, ...

How metastases develop in the liver

ELSE PRESS RELEASES FROM THIS DATE:

LAST 30 PRESS RELEASES: