Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mechanism found that ’protects’ aggressive melanoma from angiogenesis inhibitors

08.10.2004


Northwestern University researchers have discovered a mechanism that may help to explain how angiogenesis inhibitors work on normal, blood vessel-forming endothelial cells, but not on insidious, aggressive melanoma cells that masquerade as endothelial-like cells by forming their own vascular networks, called "vasculogenic mimicry."



Mary J. C. Hendrix, professor of pediatrics at Northwestern University Feinberg School of Medicine and president and scientific director of the Children’s Memorial Research Center, led the study, results of which were published in the Oct. 6 issue of the Journal of the National Cancer Institute. Hendrix and her laboratory team are also members of The Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

Hendrix and colleagues found that endostatin and two other angiogenesis inhibitors, which prevent new blood vessel growth that supports the spread of cancerous tumors, were effective in blocking endothelial cell formation of vascular networks, but were unable to prevent vascular networks formed by melanoma cells.


Further experiments showed that endothelial cells have more endostatin receptors than melanoma cells, suggesting a mechanistic basis for the differential response of the two cell types to angiogenesis inhibitors. Findings from the study may contribute to the development of new cancer therapies that target both angiogenesis and tumor cell vasculogenic mimicry. Moreover, because vasculogenic mimicry has been reported in several other tumor types, including breast, prostatic, ovarian and lung cancer, these findings may offer new insights for designing rational antivascular therapies in other forms of cancer, Hendrix said.

In the past decade, many new angiogenesis inhibitors have been identified, and several have been shown effective against tumor growth in laboratory experiments. However, results of early clinical trials with these inhibitors have not yet paralleled the success achieved in animal models. In their recent experiments, Hendrix and co-researchers examined effects of three angiogenesis inhibitors with different specificities (anginex, TNP-470, and endostatin) on vasculogenic mimicry in human melanoma cells and compared the results with effects on human endothelial cells.

Endothelial cell growth and migration were markedly inhibited by anginex, TNP-470 and endostatin, while the melanoma cells were relatively unaffected. The scientists subsequently investigated whether endothelial cells and melanoma cells expressed different levels of two newly discovered receptors (alpha 5 beta 1 integrin and heparin sulfate proteoglycan 2) for the angiogenesis inhibitor endostatin. Results showed that endothelial cells have significantly higher levels of these receptors.

"The differential response of endothelial cells and melanoma cells to angiogenesis inhibitors in our study may provide additional clues about the mechanistic interactions between endothelia and proliferating tumors and suggest additional targets for antivascular and antiangiogenic drug therapy," Hendrix said.

Hendrix’s co-researchers on this study were: Richard E. B. Seftor; Elizabeth A. Seftor; Angela R. Hess; Lynn M. Gruman; and Dawn A. Kirschmann, Children’s Memorial Research Center, Northwestern University Feinberg School of Medicine and The Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Daisy W.J. van der Schaft, and Arjan W. Griffioen are affiliated with the Research Institute for Growth and Development, Maastricht, The Netherlands. Yumi Yokoyama is with the University of Minnesota, Minneapolis.

Elizabeth Crown | EurekAlert!
Further information:
http://www.northwestern.edu

More articles from Life Sciences:

nachricht Newly designed molecule binds nitrogen
23.02.2018 | Julius-Maximilians-Universität Würzburg

nachricht Atomic Design by Water
23.02.2018 | Max-Planck-Institut für Eisenforschung GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Attoseconds break into atomic interior

A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.

In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...

Im Focus: Good vibrations feel the force

A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.

By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...

Im Focus: Developing reliable quantum computers

International research team makes important step on the path to solving certification problems

Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Basque researchers turn light upside down

23.02.2018 | Physics and Astronomy

Finnish research group discovers a new immune system regulator

23.02.2018 | Health and Medicine

Attoseconds break into atomic interior

23.02.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>