Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Molecular change occurring during brain tumor progression also evident in breast cancer

04.05.2005


A molecular change that takes place during the progression of malignant brain tumors also occurs in breast cancer, according to a study conducted at Cedars-Sinai’s Maxine Dunitz Neurosurgical Institute. The shift appears to be part of a process that enables tumors to develop the new blood vessels they need to grow rapidly, migrate and invade other tissue.



Although the switch is evident even in an early stage of breast cancer when cells are proliferating but not infiltrating normal tissue, it becomes more pronounced as the cancer progresses to the invasive stage. Therefore, the genes involved and the proteins they produce may become markers that physicians can use to determine disease progression and patient prognosis. They also may become targets for new therapies.

The switch affects proteins called laminins, which are components of the "basement membrane" of blood vessels, a thin mesh-like structure beneath the cells of the blood vessel surface (epithelium). Although the surface cells and the basement membrane are distinct entities, they affect each other through biochemical interactions. In fact, the cells actually influence the composition of the basement membrane, and the membrane, in addition to serving as a scaffold for cell attachment, regulates cell behavior, proliferation and migration.


The laminin molecule is composed of three chains -- designated alpha (£), beta (£]) and gamma (£^) -- that are linked together in various combinations to form 15 known isoforms or types of laminin. Each isoform has distinct characteristics and functions. Isoforms are known to change in normal tissues at various stages of development but they also have been found to shift in the presence of several invasive cancers. This shift coincides with blood vessel changes that encourage tumor growth and metastasis.

Over the past several years, Cedars-Sinai researchers published several articles related to their findings that the beta chain of laminins changed as brain tumors called glioblastoma multiforme progressed. Specifically, laminin-9 (£4£]2£^1) switched to laminin-8 (£4£]1£^1). Not only did the change occur, but as a brain tumor’s grade advanced, the expression of laminin-8 increased significantly.

Now, in their study of breast cancer, the researchers documented for the first time that laminin-9 switched to laminin-8, and laminin-11 (£5£]2£^1) switched to laminin-10 (£5£]1£^1) as non-invasive ductal carcinoma in situ progressed to the invasive ductal carcinoma (IDC), the type of breast cancer that accounts for about 80 percent of cases. The shift in these laminins and the presence of another isoform (laminin-2) also were seen in breast cancer cells that had metastasized to the brain.

"Although the exact mechanism causing these shifts has not yet been defined, the overexpression of laminin-2, laminin-8 and laminin-10 strongly relates to the development of breast cancer-induced neovascularization and tumor progression," said Keith L. Black, M.D., director of the Maxine Dunitz Neurosurgical Institute and one of the paper’s authors. "Determining the relative expression of £]1 to £]2 chains may be useful in diagnosing the stage and progression of breast cancer, predicting additional tumor growth and metastasis, and determining patient prognosis."

An aggressive tumor would quickly outgrow its source of nutrients and oxygen if not for the interaction between the blood vessel cells and the basement membrane to ensure a constantly renewing supply of small vessels, said Black, who directs the medical center’s Division of Neurosurgery and the Comprehensive Brain Tumor Program. But in one of their laboratory studies of brain tumor tissue, the researchers were able to reduce tumor cells’ ability to invade neighboring tissue by blocking the expression of the laminin-8 gene.

"Like malignant brain tumors, primary and metastatic breast tumors depend on angiogenesis, the tumor-driven creation of new blood vessels. Now we have found that similar molecular changes happen in highly vascular and invasive tumors such as breast and brain cancers," said Julia Y. Ljubimova, M.D., Ph.D., research scientist and senior author of the article. "Anti-angiogenic therapy that seeks to impede the development of the tumor’s vascular network is one of the relatively new and promising approaches in the treatment of solid tumors. The molecular mechanisms that contribute to tumor proliferation may prove to be targets for therapeutic intervention."

"The importance of the present paper is that this is the first demonstration of specific laminin isoform changes in pre-cancerous (ductal carcinoma in situ) and invasive ductal carcinoma as well as its metastases, in comparison with normal breast tissues," said Shikha Bose, M.D., an expert breast pathologist who participated in the study. "ƒÒ1 chain of laminin-2, -8 and -10 is detected in newly formed tumor vessels and might be important predictors for patient outcome."

Sandy Van | EurekAlert!
Further information:
http://www.cedars-sinai.edu

More articles from Life Sciences:

nachricht During HIV infection, antibody can block B cells from fighting pathogens
14.08.2018 | NIH/National Institute of Allergy and Infectious Diseases

nachricht First study on physical properties of giant cancer cells may inform new treatments
14.08.2018 | Brown University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

Im Focus: Lining up surprising behaviors of superconductor with one of the world's strongest magnets

Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur

What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...

Im Focus: World record: Fastest 3-D tomographic images at BESSY II

The quality of materials often depends on the manufacturing process. In casting and welding, for example, the rate at which melts solidify and the resulting microstructure of the alloy is important. With metallic foams as well, it depends on exactly how the foaming process takes place. To understand these processes fully requires fast sensing capability. The fastest 3D tomographic images to date have now been achieved at the BESSY II X-ray source operated by the Helmholtz-Zentrum Berlin.

Dr. Francisco Garcia-Moreno and his team have designed a turntable that rotates ultra-stably about its axis at a constant rotational speed. This really depends...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

 
Latest News

'Building up' stretchable electronics to be as multipurpose as your smartphone

14.08.2018 | Information Technology

During HIV infection, antibody can block B cells from fighting pathogens

14.08.2018 | Life Sciences

First study on physical properties of giant cancer cells may inform new treatments

14.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>