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 Building blocks for new medications: the University of Graz is seeking a technology partner
19.03.2019 | Karl-Franzens-Universität Graz

nachricht Scientists find new approach that shows promise for treating cystic fibrosis
14.03.2019 | NIH/National Heart, Lung and Blood Institute

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: Stellar cartography

The Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI) at the Large Binocular Telescope (LBT) in Arizona released its first image of the surface magnetic field of another star. In a paper in the European journal Astronomy & Astrophysics, the PEPSI team presents a Zeeman- Doppler-Image of the surface of the magnetically active star II Pegasi.

A special technique allows astronomers to resolve the surfaces of faraway stars. Those are otherwise only seen as point sources, even in the largest telescopes...

Im Focus: Heading towards a tsunami of light

Researchers at Chalmers University of Technology and the University of Gothenburg, Sweden, have proposed a way to create a completely new source of radiation. Ultra-intense light pulses consist of the motion of a single wave and can be described as a tsunami of light. The strong wave can be used to study interactions between matter and light in a unique way. Their research is now published in the scientific journal Physical Review Letters.

"This source of radiation lets us look at reality through a new angle - it is like twisting a mirror and discovering something completely different," says...

Im Focus: Revealing the secret of the vacuum for the first time

New research group at the University of Jena combines theory and experiment to demonstrate for the first time certain physical processes in a quantum vacuum

For most people, a vacuum is an empty space. Quantum physics, on the other hand, assumes that even in this lowest-energy state, particles and antiparticles...

Im Focus: Sussex scientists one step closer to a clock that could replace GPS and Galileo

Physicists in the EPic Lab at University of Sussex make crucial development in global race to develop a portable atomic clock

Scientists in the Emergent Photonics Lab (EPic Lab) at the University of Sussex have made a breakthrough to a crucial element of an atomic clock - devices...

Im Focus: Sensing shakes

A new way to sense earthquakes could help improve early warning systems

Every year earthquakes worldwide claim hundreds or even thousands of lives. Forewarning allows people to head for safety and a matter of seconds could spell...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International Modelica Conference with 330 visitors from 21 countries at OTH Regensburg

11.03.2019 | Event News

Selection Completed: 580 Young Scientists from 88 Countries at the Lindau Nobel Laureate Meeting

01.03.2019 | Event News

LightMAT 2019 – 3rd International Conference on Light Materials – Science and Technology

28.02.2019 | Event News

 
Latest News

Levitating objects with light

19.03.2019 | Physics and Astronomy

New technique for in-cell distance determination

19.03.2019 | Life Sciences

Stellar cartography

19.03.2019 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>