Science

Metadherin mediates lung metastasis of breast tumors

Last Updated: 2004-04-21 11:03:44 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Metadherin, a cell surface protein overexpressed in breast tumors, mediates their metastasis to the lung, according to a report in the April issue of Cancer Cell.

Breast cancer spreads first to the lungs and liver, the authors explain, but many of the factors that contribute to organ-specific metastasis have yet to be identified.

Dr. Darren M. Brown and Dr. Erkki Ruoslahti from The Burnham Institute in La Jolla, California used in vivo phage screening of cDNA from metastatic breast carcinoma to identify tumor cell surface molecules that mediate breast cancer metastasis.

The authors isolated a protein they called metadherin (for metastasis adhesion protein) that caused the phage to home specifically to lung microvasculature after intravenous injection in mice.

Seventeen of 31 human breast adenocarcinomas stained positive for antibodies to metadherin, the report indicates, but 18 of 20 normal human breast tissue samples stained negative for metadherin.

When co-injected with breast cancer cells, anti-metadherin antibody or metadherin siRNA inhibited lung metastasis by 40% and 80%, respectively, the researchers note.

Testing patients' tumors for "combinations of new markers, such as metadherin, may make it possible for the physician to better determine how likely a given tumor is to spread," Dr. Ruoslahti told Reuters Health. "The aggressiveness of the therapy can then be adjusted accordingly."

"The use of metadherin testing in predicting the aggressiveness of a [breast] cancer may be relatively quick to introduce into the clinic," Dr. Ruoslahti said. "As far as therapeutic applications, it is hard to tell. There is a lot of basic research to be done."

"As metadherin is greatly overexpressed in breast cancer, we hope to show that targeting metadherin with antibodies, or other by other means, can reduce tumor growth in animals," Dr. Ruoslahti concluded. "If positive, such results could open up new treatment possibilities."

Cancer Cell 2004;5:365-374.