Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

T-Cadherin Affects Blood Vessel Growth in Breast Cancer, Hormone from Fat Cells May Play a Role

08.04.2008
Researchers at the Burnham Institute for Medical Research (Burnham) may have found a new option for targeted breast cancer therapy by showing the link between a certain protein and the formation and development of blood vessels that feed breast tumors.

Like mortar between bricks in a wall, T-cadherin is a protein that helps cells stick together and collectively form tissues. Cancer cells that loosen their adhesive tissue bonds stop producing T-cadherin, and in tumors, only the blood vessels that supply oxygen and nutrients express this protein.

Now, Barbara Ranscht, Ph.D., and Robert Oshima, Ph.D., at Burnham have led a team that developed the first living model to study this protein’s effect on tumor angiogenesis by creating a strain of mice that develops spontaneous mammary gland tumors in the absence of T-cadherin. Their results appeared March 1 in Cancer Research.

“Evidence of T-cadherin’s role in vascularization has been somewhat controversial,” explains Dr. Ranscht, senior author of the study, which includes Drs. Lionel Hebbard and Michèle Garlatti from the Burnham Institute as equally contributing first authors and Drs. Robert Cardiff and Lawrence Young as collaborators from the University of California, Davis. “But our knockout model clearly shows that T-cadherin plays a role in promoting tumor vascularization, with implications for tumor growth and animal survival.”

The tumor model developed in Dr. Ranscht’s laboratory shows that loss of T-cadherin slows down tumor growth and improves survival compared to controls where T-cadherin is present: The absence of T-cadherin delays tumor growth by an average of 10 days, decreases tumor size, and apoptosis markers, indicators of cell suicide, are six times higher. The tumor-bearing knockouts live an average of 18.5 days longer than their wild-type counterparts, which translates into approximately 18 months of human life span.

The normal models in the study developed solid adenocarcinoma breast tumors, whereas the knockouts formed poorly-differentiated breast tumors with fewer blood vessels. When the adenocarcinoma tumors were transplanted into normal and T-cadherin-deficient mammary glands the knockouts were deficient in growing new blood vessels to the graft.

Stunting blood vessel growth restricts tumors and prolongs survival—a strategy behind anti-angiogenesis cancer drugs like Avastin—so these results were somewhat expected, says Dr. Ranscht. “But what surprised us,” she adds, “was that even though our models survived longer, their tumor pathology worsened.” Without T-cadherin-mediated vascularization, breast cancer cells consistently metastasized to the lungs, and this did not happen in the control mice where the tumors were highly vascularized.

The reasons for this trend are not clear: loose connections between vascular cells may make it easier for tumor cells to break off and enter the blood stream, or low blood flow and oxygen levels in the tumor environment may cause free radicals to build up, spurring further mutations and malignancy.

Either way, says Dr. Ranscht, “Our work provides a cautionary example that restricting tumor angiogenesis might result in more aggressive disease in the long run. Thus, anti-angiogenic therapies should be carefully evaluated, because if growth at the primary tumor site slows but at the same time women develop more aggressive, metastatic cancers, then it is imperative to develop and add treatments that prevent this.”

This study also showed for the first time in a living model that T-cadherin is essential for binding adiponectin, a hormone produced by fatty tissue that is released in inversely proportional amounts to body fat. Adiponectin has a protective effect against metabolic diseases including diabetes, hypertension, heart disease, and stroke; now for the first time it is linked in a living model with vascular function, a relationship that the Burnham team is still exploring. “While the link between obesity and breast cancer is complex, this study shows that in the mouse, T-cadherin sequesters much of the adiponectin and thus provides a conceptual link between obesity and breast cancer” notes Dr. Oshima.

This research is supported by grants from the National Institutes of Health and the Department of Defense.

About Burnham Institute for Medical Research
Burnham Institute for Medical Research uses an entrepreneurial, collaborative approach to medical research to reveal the fundamental molecular causes of disease and devise the innovative therapies of tomorrow. The Institute is organized into five research centers: a National Cancer Institute-designated Cancer Center; the Del E. Webb Center for Neurosciences, Aging and Stem Cell Research; an Infectious and Inflammatory Disease Research Center; a Diabetes and Obesity Research Center; and the Sanford Children’s Health Research Center. Thanks to the quality of its faculty members, Burnham ranks among the top 25 organizations worldwide (according to the Institute for Scientific Information) for its research impact and among the top four research institutes nationally for NIH grant funding. Burnham is a nonprofit, public benefit corporation headquartered in La Jolla, California, with campuses in Orlando, Florida and Santa Barbara, California.

Andrea Moser | EurekAlert!
Further information:
http://www.burnham.org

More articles from Health and Medicine:

nachricht New way to target advanced breast cancers
24.09.2018 | Jackson Laboratory

nachricht Neutrons produce first direct 3D maps of water during cell membrane fusion
21.09.2018 | DOE/Oak Ridge National Laboratory

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Scientists present new observations to understand the phase transition in quantum chromodynamics

The building blocks of matter in our universe were formed in the first 10 microseconds of its existence, according to the currently accepted scientific picture. After the Big Bang about 13.7 billion years ago, matter consisted mainly of quarks and gluons, two types of elementary particles whose interactions are governed by quantum chromodynamics (QCD), the theory of strong interaction. In the early universe, these particles moved (nearly) freely in a quark-gluon plasma.

This is a joint press release of University Muenster and Heidelberg as well as the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt.

Then, in a phase transition, they combined and formed hadrons, among them the building blocks of atomic nuclei, protons and neutrons. In the current issue of...

Im Focus: Patented nanostructure for solar cells: Rough optics, smooth surface

Thin-film solar cells made of crystalline silicon are inexpensive and achieve efficiencies of a good 14 percent. However, they could do even better if their shiny surfaces reflected less light. A team led by Prof. Christiane Becker from the Helmholtz-Zentrum Berlin (HZB) has now patented a sophisticated new solution to this problem.

"It is not enough simply to bring more light into the cell," says Christiane Becker. Such surface structures can even ultimately reduce the efficiency by...

Im Focus: New soft coral species discovered in Panama

A study in the journal Bulletin of Marine Science describes a new, blood-red species of octocoral found in Panama. The species in the genus Thesea was discovered in the threatened low-light reef environment on Hannibal Bank, 60 kilometers off mainland Pacific Panama, by researchers at the Smithsonian Tropical Research Institute in Panama (STRI) and the Centro de Investigación en Ciencias del Mar y Limnología (CIMAR) at the University of Costa Rica.

Scientists established the new species, Thesea dalioi, by comparing its physical traits, such as branch thickness and the bright red colony color, with the...

Im Focus: New devices based on rust could reduce excess heat in computers

Physicists explore long-distance information transmission in antiferromagnetic iron oxide

Scientists have succeeded in observing the first long-distance transfer of information in a magnetic group of materials known as antiferromagnets.

Im Focus: Finding Nemo's genes

An international team of researchers has mapped Nemo's genome

An international team of researchers has mapped Nemo's genome, providing the research community with an invaluable resource to decode the response of fish to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

"Boston calling": TU Berlin and the Weizenbaum Institute organize a conference in USA

21.09.2018 | Event News

One of the world’s most prominent strategic forums for global health held in Berlin in October 2018

03.09.2018 | Event News

4th Intelligent Materials - European Symposium on Intelligent Materials

27.08.2018 | Event News

 
Latest News

Matter falling into a black hole at 30 percent of the speed of light

24.09.2018 | Physics and Astronomy

NASA balloon mission captures electric blue clouds

24.09.2018 | Earth Sciences

New way to target advanced breast cancers

24.09.2018 | Health and Medicine

VideoLinks
Science & Research
Overview of more VideoLinks >>>