December 13, 2010

Defective Cell Surface “Glue” Is Key To Tumor Invasion

A remarkable discovery into how tumor cells invade normal tissue should lead to vital diagnostic tools and help develop strategies to stop the spread of cancer cells. A new study by scientists at the Montreal Neurological Institute and Hospital of McGill University reveals that the surface of aggressive tumor cells lack the strong molecular "Ëœglue' responsible for binding normal cells together. This allows tumor cells to break away, detach from their neighbors, and spread to other regions of the body.

Certain proteins, called cadherins, are located on the surface of cells and play a vital role in cell adhesion or "Ëœgluing' cells together, ensuring the proper organization of tissue.  What happens to the cells and the "Ëœglue' that binds them in tumor growth and metastases is poorly understood.  "We were concerned that previous research showed that N-cadherin, an adhesive molecule, was important for both normal tissue organization, as well as tumor metastasis," says Dr. David Colman, Director of The Neuro and corresponding author of the study.  "We therefore decided to further investigate this apparent paradox."

The team studied the levels of N-cadherin on tumor cell surfaces.  "Our study shows that a non-adhesive form of N-cadherin, termed proNcad is present in a much higher proportion on the surfaces of the most invasive melanoma, brain tumor cells, breast cancer and prostate tumor cells, compared to less invasive tumor cells." says Dr. Deborah Maret, research associate and lead author. This non-adhesive form of N-cadherin never reaches the cell surface in normal tissues.

"It appears that although total N-cadherin levels remain constant, the higher levels of the non-adhesive proNcad promote detachment, tumor cell migration and invasion," adds Dr. Maret. "This supports an overall conclusion that non-adhesive (proNcad) and adhesive (Ncad) forms of cadherins co-exist on tumor cell surfaces, but it is the ratio between these functionally opposite molecules that directly dictates the invasion potential of tumor cells." Because the differences between the two forms of cadherin are so small, previous studies have missed detecting the non-adhesive proNcad form on tumor cell surfaces. Hence it was assumed that all Ncad on the tumor cell surface was of the adhesive type. "We were astounded that this was not the case at all," says Dr. Colman.

"As a brain tumor surgeon, I know that stopping cancer cells from migrating is critical for patient survival," says Dr. Rolando Del Maestro, Director of The Brain Tumor Research Centre and a co-author on the study. "We are determined to improve treatment options for patients. We have already introduced new neurosurgical methods and technologies that are unique in North America and are spearheading multidisciplinary initiatives to advance brain tumor research."

Determining the ratios of Ncad and proNcad on the cell surface may serve as a tremendously valuable tool for the staging and progression of malignant tumors. The findings may also shed light on new treatment strategies to arrest the metastatic spread of invasive tumor cells.

The study was published in this week's issue of the journal Neoplasia, and was funded by the Canadian Institutes of Health Research; a Richard H Tomlinson Doctoral Fellowship; the Maggie De Fontes Foundation; the Brain Tumor Foundation of Canada; the National Institutes of Health, The Raymonde and Tony Boeckh Fund, Goals for Lily Fund, the Alex Pavanel Family Fund, and the Franco Di Giovanni Brain Tumor Research Fund.

About the Montreal Neurological Institute and Hospital

The Montreal Neurological Institute and Hospital "” The Neuro, is a unique academic medical centre dedicated to neuroscience. The Neuro is a research and teaching institute of McGill University and forms the basis for the Neuroscience Mission of the McGill University Health Centre. Founded in 1934 by the renowned Dr. Wilder Penfield, The Neuro is recognized internationally for integrating research, compassionate patient care and advanced training, all key to advances in science and medicine. Neuro researchers are world leaders in cellular and molecular neuroscience, brain imaging, cognitive neuroscience and the study and treatment of epilepsy, multiple sclerosis and neuromuscular disorders. The Montreal Neurological Institute was named as one of the Seven Centres of Excellence in Budget 2007, which provided the MNI with $15 million in funding to support its research and commercialization activities related to neurological disease and neuroscience.


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