Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers define mechanism that enables stem cells to track migrating brain tumor cells

05.05.2004


Because they target and track deadly brain tumor cells – even those that migrate within the brain – neural stem cells appear to be effective "delivery systems" to transport cancer-killing gene and immune products. But not all neural stem cells take on this tracking role.



Now researchers at Cedars-Sinai’s Maxine Dunitz Neurosurgical Institute, using mouse and human cells, have defined a subset of neural stem cells that have this tumor-tracking potential. They also have identified a biochemical mechanism that appears to govern the homing behavior. Their results appear in the May/June issue of the journal Neoplasia.

The prognosis for patients with malignant brain tumors called gliomas is extremely poor. Those with glioblastoma multiforme, the most aggressive of the gliomas, usually have a life expectancy of only months from the time of diagnosis. Survival for two years is extremely rare, even with aggressive treatment. Chemotherapy and radiation therapy have only minimal impact, and because gliomas have poorly defined borders, with glioma cells intermingling with healthy brain tissue, complete surgical removal is nearly impossible. Furthermore, cancer cells migrate away from the main tumor to form satellites that often escape treatment and lead to recurrence.


"We have previously demonstrated the uncanny ability of neural stem cells to seek out and destroy satellites of tumor cells in the brain. Now we know at least one component of tumor cells that is attracting neural stem cells toward them. With this knowledge, we hope to expedite the translation of this powerful and novel strategy for the clinical benefit of patients with brain tumors," said John S. Yu, senior author of the study and co-director of the Comprehensive Brain Tumor Program at Cedars-Sinai.

"Given the very poor prognosis associated with high-grade gliomas, there is an urgent need to develop novel therapies that can be translated into clinical practice. The use of neural stem cells as therapeutic delivery vehicles has offered encouraging results in pre-clinical models," said Keith L. Black, MD, director of the Institute and of Cedars-Sinai’s Division of Neurosurgery and the Comprehensive Brain Tumor Program. "It is exciting to begin to identify and describe the mechanisms that govern this tracking behavior. This obviously is fundamental to advancing our earlier observations toward successful treatment."

Within the past several years, Cedars-Sinai researchers have published animal and laboratory studies showing that neural stem cells – "immature" cells that have the potential to differentiate into any of several types of central nervous system cells – have the ability to track glioma cells as they migrate. In recently published work, the researchers genetically engineered tumor-tracking stem cells to secrete interleukin 12, which elicited a local immune response that attacked cancer cells at the tumor site and in the satellites. They also engineered neural stem cells to deliver a protein that causes the death of cancer cells without harming normal cells.

While these and similar studies suggest that cancer-killing immune system components can be piggybacked with neural stem cells to track and attack glioma cells even as they migrate, the mechanisms responsible for this tracking ability have remained a mystery.

Although many of the stem cells transplanted into tumors have demonstrated robust migratory activity and tumor tracking capabilities, a significant number have remained at the injection site. The injections have consisted of stem cells at various levels of differentiation – some still "uncommitted" as to the type of cells they would eventually become, some developing into neurons, and some becoming glial cells.

"We hypothesized that the tumor-tracking capacity was likely exhibited by a specific subpopulation of progenitor cells at a particular stage of differentiation," said Dr. Yu. "Our findings clearly point to astrocytic progenitors as the candidate cells exhibiting tumor-tracking capacity within transplanted neural stem cells."

Specifically, he said, the candidate cells appear to be at an advanced stage of differentiation but are not yet mature astrocytes, a subcategory of glial cells. Astrocytes are comparatively large, star-shaped cells that influence the activity of neurons and provide structure for the cells of the brain.

The researchers also found that these astrocytic precursors expressed significant levels of a "chemokine receptor" called CXCR4. Chemokines are proteins that are produced and released by a variety of types of cells. Like chemical magnets, in a sense, they attract cells that have compatible receptors on their surfaces. When the proteins bind at the receptors, they activate internal signaling pathways that cause a cell to behave in a certain way.

CXCR4 is known to govern cellular migration and homing in a variety of cell types, including neuronal and glial precursors in the developing brain. The only known chemokine that binds with CXCR4 is stromal-cell derived factor-1 (SDF-1). High-grade gliomas have recently been found to secrete significant levels of SDF-1.

The authors conclude that SDF-1 secreted by glioma cells migrating away from a tumor attracts CXCR4 and the neural stem cells upon which these receptors reside. In fact, when these receptors were blocked from interacting with SDF-1 in the laboratory, neural stem cell migration toward glioma cells was inhibited, confirming the importance of the CXCR4/SDF-1 pathway.

"The identification of CXCR4 as a key element governing the process of neural precursor migration toward glioma cells may allow for more efficient isolation of potential tumor-tracking cells, which may hasten the therapeutic testing of glioma-tracking neural precursors in the clinical setting," said Dr. Black, who holds the Ruth and Lawrence Harvey Chair in Neuroscience at Cedars-Sinai.


This study was supported in part by National Institutes of Health grant NS02232 to Dr. Yu.

Cedars-Sinai is one of the largest nonprofit academic medical centers in the Western United States. For the fifth straight two-year period, it has been named Southern California’s gold standard in health care in an independent survey. Cedars-Sinai is internationally renowned for its diagnostic and treatment capabilities and its broad spectrum of programs and services, as well as breakthroughs in biomedical research and superlative medical education. The Medical Center ranks among the top 10 non-university hospitals in the nation for its research activities.

Sandra Van | Van Communications
Further information:
http://www.csmc.edu/

More articles from Life Sciences:

nachricht Unique genome architectures after fertilisation in single-cell embryos
30.03.2017 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

nachricht Transport of molecular motors into cilia
28.03.2017 | Aarhus 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: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

'On-off switch' brings researchers a step closer to potential HIV vaccine

30.03.2017 | Health and Medicine

Penn studies find promise for innovations in liquid biopsies

30.03.2017 | Health and Medicine

An LED-based device for imaging radiation induced skin damage

30.03.2017 | Medical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>