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October 31, 2005

Cancer cell communication exposed

Topics: Medicine
The Eph family of receptor tyrosine kinases and their ephrin ligands are mediators of cell-cell communication. Cleavage of ephrin-A2 by the ADAM10 membrane metalloprotease enables contact repulsion between Eph- and ephrin-expressing cells.

... Being able to regulate the communication between these cell surface molecules, which are found at high levels in many human cancers, by preventing the function of ADAM, may actually stop the growth and spread of tumours.

Scientists at Monash University and the Sloan Kettering Cancer Center in New York, have discovered the structure of the molecular switch that controls communication between tumour cells, and that understanding of how communication between cancer cells is controlled, offers promise for new treatment options for malignant tumors.
Senior research fellow Dr Martin Lackmann from Monash's Department of Biochemistry and Molecular Biology is part of the team that has discovered the structure of the molecular switch that controls communication between tumour cells. The "switch" involves a cell-surface protease called ADAM10 that regulates the signals that promote tumour growth and motility of cancer cells.

Understanding the structure of the ADAM10 molecule provides a basis for developing pharmaceutical drugs to inhibit tumour growth and metastasis - the spreading of cancerous tumour cells throughout the body.

Dr Lackmann said the findings, published in the latest issue of the international journal /Cell,/ had altered the perception of the way cell signalling molecules - such as growth factor and cell positioning receptors - communicate and regulate processes such as cell adhesion and motility.

"While the critical role of ADAM10 in tumour growth and spreading was clear for a long time, we were unaware how ADAM 10 achieved its control on the function of important cell surface molecules, such the Eph and Ephrin cell positioning proteins," Dr Lackmann said.

"We discovered that ADAM10 specifically recognised only Eph and Ephrin molecules that were actively engaged in signalling, and by manipulating the ADAM structure were able to interfere with this molecular recognition and arrest signalling.

"Being able to regulate the communication between these cell surface molecules, which are found at high levels in many human cancers(emphasis added), by preventing the function of ADAM, may actually stop the growth and spread of tumours."

Related reading: Review Diverse Roles of Eph Receptors and Ephrins in the Regulation of Cell Migration and Tissue Assembly

EPH RECEPTOR SIGNALLING CASTS A WIDE NET ON CELL BEHAVIOUR

Posted by Richard at October 31, 2005 2:38 PM



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