After a path to a potential therapy for NF2, a rare Tumor disorder

The proteins that cells equipped with a sense of personal space can lead to a therapeutic target for Neurofibromatosis Type 2 (NF2), a hereditary cancer disorder, according to researchers at the Wistar Institute. Their findings, which in the April 12 issue of the journal cancer cell, can have far-reaching consequences for NF2 and related cancers such as mesothelioma.

The researchers describe, for the first time, that Merlin, the protein that is encoded within the gene NF2 communicates with called angiomotin. This link between Merlin and angiomotin also brings two important information networks in cells, both of which have been implicated in numerous forms of cancer. It is a connection, the researchers say, between the sensors that detect interactions between cells and signaling networks that drive cell division.

"Angiomotin is required for movement of cells that form new blood vessels, so it's fascinating to see it so closely associated with merlin, the product of the NF2 gene, loss of that to the formation of tumour leads," said Joseph Kissil, Ph.d., senior author of the study and associate professor in the molecular and cellular oncogenesis program of the Wistar Institute Cancer Center. "The discovery opens a potential new method for the treatment of NF2 by an attack on the tumor cells directly and through hunger, a strategy which is already working in certain cancer therapies."

"Drugs such as trade name Avastin, for example, targeting the growing blood vessels," said Kissil, "but what makes angiomotin a tempting goal is that it is used by both the blood vessels and the growing tumor cells need nutrients these blood vessels offer."

NF2 is a genetic disorder caused by a mutation in both copies of someones NF2 gene. it occurs in about one in 30,000 people, and it is usually hereditary. NF2 is generally represented as benign tumours in the nervous system of young adults, who often cause of deafness as tumors affect the auditory nerves. While the tumors are usually benign, can ultimately more malignant tumors arise. Furthermore, even the benign tumors often cause debilitating pain as they spread across the nervous system. There is currently no treatment for NF2 other than surgery to remove tumors as they are displayed.

Mutations in the gene NF2 disrupt the function of the gene of protein product, Merlin, which is part of a comprehensive molecular signaling pathway that regulates how cells grow and divide. These pathways are related to information channels and disrupting a protein can alter the function of other proteins both upstream and downstream along the Canal. Merlin is especially interesting for cancer biologists, such as the mutations have been found in approximately half of all cases of the deadly lung cancer mesothelioma, and in some cases of thyroid gland, bladder, and other forms of cancer.

According to Merlin Kissil stops normal cells grow once they get in contact with adjacent cells. I.e., binds to the Merlin angiomotin on "links," areas where cells in contact with each other. When connected, relate the interacting proteins a signal to the cell, in essence, orders to stop further growth and traffic. It is a way to coordinate their growth of cells within a tissue. Cancer cells, for example, often do not have that feeling of inhibition, and they will continue to grow uncontrolled.

The Kissil laboratory wants to continue their exploration of angiomotin as a potential therapeutic target for the treatment of NF2, and also look at the role of angiomotin in other types of cancer known to be affected by NF2 mutations.

Comments:

Funding for this study was provided partly by means of a subsidy Kissil of the National Cancer Institute of the National Institutes of Health. The study was supported by a Young Investigator Award from the children's Tumor Foundation to Chunling Yi, Ph.d., a post-doctoral fellow in the laboratory Kissil.

Wistar employees also include research assistants Scott Troutman and Neepa Christian; graduate students Daniela Fera and Jacqueline l. Avila; and Wistar professors David w. Speicher, Ph.d. and Ronen Marmorstein, Ph.d. co-authors include Akihiko Shimono, Ph.d., of the cancer Science Institute of Singapore at the National University of Singapore; Lars Holmgren, Ph.d., and Nathalie l. Persson of the Karolinska Institute in Stockholm, Sweden; and Anat Stemmer-Rachamimov, M.D., of Massachusetts General Hospital in Boston.

Source:
Greg Lester
The Wistar Institute

Drug-information on trade name Avastin.