Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Enzyme helps prepare lung tissue for metastatic development

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."

Jain is the Cook Professor of Radiation Oncology (Tumor Biology), Duda an assistant professor of Radiation Oncology, and Fukumura an associate professor of Radiation Oncology at Harvard Medical School. The lead author of the PNAS paper is Sachie Hiratsuka, MD, PhD, of the Steele Laboratory at MGH. Additional co-authors are Shom Goel, MD, and Walid Kamoun, PhD, Steele Lab; and Yoshiro Maru, MD, PhD, Tokyo Women's Medical University. The study was supported by grants from the National Institutes of Health and other funders.

Celebrating the 200th anniversary of its founding in 1811, Massachusetts General Hospital is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of nearly $700 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine.

Sue McGreevey | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht ‘Farming’ bacteria to boost growth in the oceans
24.10.2016 | Max-Planck-Institut für marine Mikrobiologie

nachricht Calcium Induces Chronic Lung Infections
24.10.2016 | Universität Basel

All articles from Life Sciences >>>

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 >>>