Navigation Links
T-cadherin affects blood vessel growth in breast cancer, hormone from fat cells may play a role
Date:4/4/2008

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 proteins 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-cadherins role in vascularization has been somewhat controversial, explains Dr. Ranscht, senior author of the study, which includes Drs. Lionel Hebbard and Michle 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. Ranschts 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 survivala strategy behind anti-angiogenesis cancer drugs like Avastinso 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.


'/>"/>

Contact: Andrea Moser
amoser@burnham.org
858-646-3146
Burnham Institute
Source:Eurekalert  

Related biology news :

1. Study finds pitching mound height affects throwing motion, injury risk
2. Gene dose affects tumor growth
3. Restless legs syndrome affects nearly 2 percent of US/UK children
4. Gender, coupled with diabetes, affects vascular disease development
5. Umbilical cord blood cell therapy may reduce signs and symptoms of Alzheimers disease
6. Umbilical cord blood cell therapy in an animal model of Alzheimers disease
7. Blood vessel protein reverses macular degeneration, diabetic retinopathy in mice
8. Diabetes makes it hard for blood vessels to relax
9. Weill Cornell team discovers how brains own tPA helps regulate blood flow to neurons
10. High blood pressure in older adults traced to genes effects in blood vessels
11. Eltrombopag effective for hepatitis C patients with low blood-platelet counts
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
T-cadherin affects blood vessel growth in breast cancer, hormone from fat cells may play a role
(Date:3/9/2017)... MELBOURNE , Australia , March ... clinical study data at the prestigious World Lung Imaging ... Dr. Andreas Fouras , was invited to deliver ... and pulmonary medicine. This globally recognised event brings together ... and share the latest developments in lung imaging. ...
(Date:3/7/2017)... , March 7, 2017   HireVue , the ... global companies identify the best talent, faster, today announced ... Sales Officer (CSO) and Diana Kucer as ... out a seasoned executive team poised to drive continued growth ... on a year of record bookings in 2017. ...
(Date:3/2/2017)... Summary This report provides all ... and its partnering interests and activities since 2010. ... The Partnering Deals and Alliance since 2010 report provides ... of the world,s leading life sciences companies. ... ensure inclusion of the most up to date deal ...
Breaking Biology News(10 mins):
(Date:3/22/2017)... LEXINGTON, Mass. , March 22, 2017   ... collections, today announced that Doctors Pathology Service ... mid-Atlantic region of the United States ... the Delaware Health Information Network (DHIN) to ... researchers. The novel program, announced in ...
(Date:3/22/2017)... , March 22, 2017   ... independent provider of product and service solutions ... that it has acquired EPL Archives, Inc., ... customers across the entire regulated product research, ... sample, document storage and ancillary services. EPL ...
(Date:3/22/2017)... , ... March 21, 2017 , ... ... , more than tripling its goal and raising over $30,000 in the first ... that grows nutritious veggies & herbs fast, easy, and affordably, anywhere. , “Simply ...
(Date:3/22/2017)... ... March 22, 2017 , ... March 22, 2017...Council for Agricultural Science and Technology, ... that utilizes technological innovation in smart, sustainable ways. Humans depend on plants for food, ... and environmental stability. This paper is the first in a series that connects science ...
Breaking Biology Technology: