Navigation Links
Enzyme helps prepare lung tissue for metastatic development
Date:2/16/2011

A Massachusetts General Hospital (MGH) study has identified a new role for an important enzyme in preparing lung tissue for the development of metastases. Published in the early edition of Proceedings of the National Academy of Sciences, the report describes how focal adhesion kinase (FAK) is involved in producing areas of vascular leakiness in lung tissue known to be part of the premetastatic process and increases expression of a molecule that attracts cancer cells to potential metastatic sites.

"Blood from all tissues of the body travels to the lungs for oxygenation, increasing the likelihood that circulating metastatic cells will interact with the lung microvasculature," says Rakesh K. Jain, PhD, director of the Steele Laboratory for Tumor Biology at MGH and senior author of the study. "Identifying factors that prepare this 'hospitable soil' for tumor formation may help us develop strategies to slow or halt that process."

In order to form metastases, cancer cells carried through the bloodstream need to find an environment that allows them to adhere and proliferate. While recent research supports the hypothesis that primary tumors secrete factors that prepare distant sites for potential metastatic development, defining the role of specific factors has been challenging. The current study investigated whether the ability of tumors in other parts of the body to induce formation of distinct areas of abnormal leakiness in lung tissue contributes to the development of metastases.

The researchers first confirmed that either the presence of an implanted tumor or infusions of factors secreted by tumors produced localized areas of leakiness in the lungs of mice. Analysis of the tumor-secreted factors identified specific molecules known to increase vascular permeability, including the angiogenesis-inducing vascular endothelial growth factor (VEGF). Metastatic cells infused into mice treated with either tumor-secreted factors or VEGF preferentially adhered to sites of leaky lung tissue, and both this attraction of tumor cells and the increase in vascular permeability were reduced by blocking VEGF activity.

Since VEGF is known to activate FAK which plays a role in cellular signaling in the endothelial cells that line pulmonary blood vessels, the researchers analyzed levels of the enzyme at the sites of induced vascular leakiness and found them to be elevated. "Blocking the activity of FAK in lung endothelial cells reduced both vascular permeability and the adhesion of metastatic cells to those tissues. Additional genetic experiments revealed that FAK produces these effects through increased local expression of the cellular adhesion molecule E-selectin," says Dai Fukumura, MD, PhD, of the Steele Lab, a co-senior author of the report.

Co-senior author Dan G. Duda, DMD, PhD, also of the Steele Lab, adds, "Anti-metastatic therapy is the ultimate frontier for cancer therapy, but existing treatments both traditional chemotherapy and newer antiangiogenesis agents have limited effectiveness in preventing the development of metastases. Our findings provide proof of principle that FAK inhibition is a valid antimetastatic strategy that should be investigated in future translational studies."


'/>"/>

Contact: Sue McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
Source:Eurekalert

Related medicine news :

1. Heart Enzymes May Predict Outcome After Bypass Surgery
2. Breathing easy: LSU biochemists offer first 3-D model of asthma-causing inflammation enzyme
3. Princess Margaret Hospital researchers identify a key enzyme that affects radiation response
4. Chaperone enzyme provides new target for cancer treatments
5. Virus might fight brain tumors better if armed with bacterial enzyme, study shows
6. Enzyme inhibition or removal may prevent or treat ischemic retinopathy
7. New clue in leukemia mystery: Researchers identify poison employed by deadly enzyme mutations
8. UH physicists study behavior of enzyme linked to Alzheimers, cancer
9. Enzyme action could be target for diabetes, heart disease treatments
10. New 3-D model of RNA core domain of enzyme telomerase may offer clues to cancer, aging
11. Intestinal enzyme helps maintain population of beneficial bacteria
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/27/2016)... ... June 27, 2016 , ... A revolution is ... emergency ambulance transport experience for the millions of people who require these medical ... the taxi industry through the use of technology. Now, SmartEMS has put forth ...
(Date:6/26/2016)... (PRWEB) , ... June 26, 2016 , ... PawPaws ... a new product that was developed to enhance the health of felines. The formula ... , The two main herbs in the PawPaws Cat Kidney Support Supplement ...
(Date:6/25/2016)... ... June 25, 2016 , ... The temporary closing of Bruton Memorial Library on June 21 due ... up a new, often overlooked aspect of head lice: the parasite’s ability to live away ... a common occurrence, but a necessary one in the event that lice have simply gotten ...
(Date:6/25/2016)... ... ... On Friday, June 10, Van Mitchell, Secretary of the Maryland Department of ... recognition of their exemplary accomplishments in worksite health promotion. , The Wellness at Work ... Symposium at the BWI Marriott in Linthicum Heights. iHire was one of 42 businesses ...
(Date:6/24/2016)... ... , ... Marcy was in a crisis. Her son James, eight, was out of control. Prone ... physically. , “When something upset him, he couldn’t control his emotions,” remembers Marcy. “If ... at my other children and say he was going to kill them. If we ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... , June 23, 2016  MedSource announced ... as its e-clinical software solution of choice.  This ... best possible value to their clients by offering ... The preferred relationship establishes nowEDC as the EDC ... for MedSource,s full-service clients.  "nowEDC has long been ...
(Date:6/23/2016)... 2016 Any dentist who has made an implant ... process. Many of them do not even offer this as ... high laboratory costs involved. And those who ARE able to ... a high cost that the majority of today,s patients would ... Parsa Zadeh , founder of Dental Evolutions Inc. and inventor ...
(Date:6/23/2016)... Ill. , June 23, 2016  In a startling report ... are failing their residents by lacking a comprehensive, proven plan to ... a definitive ranking of how states are tackling the worst ... to only four states – Kentucky , ... Vermont . Of the 28 failing states, three ...
Breaking Medicine Technology: