Cancer Research Lab

A team of scientists at Memorial Sloan-Kettering Cancer Center in New York has identified several endogenous human microRNAs that suppress breast cancer metastasis to lung and bone — the two main sites of metastatic spread of breast carcinoma.

In the January 10 issue of Nature, Dr. Sohail F. Tavazoie and colleagues report that their search for “general regulators of cancer metastasis has yielded a set of microRNAs for which expression is specifically lost as human breast cancer cells develop metastatic potential.”

Restoring the expression of these microRNAs, by means of plasmid vectors, in malignant cells suppresses lung and bone metastasis by human cancer cells in vivo, they found.

In mice with human breast cancer tumors, restoration of one microRNA, miR-126, reduced overall tumor growth and proliferation, whereas restoration of miR-335 inhibited metastatic cell invasion.

Dr. Tavazoie and colleagues also observed that expression of miR-126 and miR-335 was lost in the majority of primary breast tumors from women who relapsed, and loss of expression of either of these two microRNAs was associated with poor survival.

In further studies, the investigators found that miR-335 suppresses metastasis by targeting a transcription factor that regulates the SOX4 group of genes responsible for cell development and migration, as well as an extracellular matrix component implicated in cell migration called tenascin C.

“The strong association of the loss of miR-335 and miR-126 expression with metastatic relapse suggests the potential for the use of these molecules in prognostic stratification of breast cancer patients in addition to conventional clinical and pathological staging markers,” the researchers write.

This research may also “enhance our ability to come up with more effective drugs to prevent or treat cancer metastasis,” Dr. Joan Massagué, the study’s senior author, added in a written statement.