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

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:

More articles from Health and Medicine:

nachricht Inflammation Triggers Unsustainable Immune Response to Chronic Viral Infection
24.10.2016 | Universität Basel

nachricht Resolving the mystery of preeclampsia
21.10.2016 | Universitätsklinikum Magdeburg

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: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Oasis of life in the ice-covered central Arctic

24.10.2016 | Earth Sciences

‘Farming’ bacteria to boost growth in the oceans

24.10.2016 | Life Sciences

Light-driven atomic rotations excite magnetic waves

24.10.2016 | Physics and Astronomy

More VideoLinks >>>