MicroRNA Reprograms Metastatic Ovarian Cancer Cells

Cancer researchers have identified a class of microRNA (miRNA) that is able to induce the transformation of metastatic ovarian cancer (OC) cells into a cell type that resembles less pathogenic primary tumor cells.

Cancer cells exist in two forms, epithelial cancer cells that constitute the primary tumor and mesenchymal cancer cells that have broken away from the primary tumor and are motile and aggressive. The transition from the epithelial cell type to the mesenchymal is called the epithelial-to-mesenchymal transition (EMT). The search for methods to control or reverse EMT is the topic of a paper published in the January 28, 2011, online edition of the journal Gynecologic Oncology.

"Primary tumors are rarely fatal,” said senior author Dr. John F. McDonald, professor of cancer research at the Georgia Institute of Technology (Atlanta, USA). "Most cancer patients succumb because the cancer metastasizes, and current chemotherapies are not designed to kill metastasizing cancer cells.”

Dr. McDonald's team worked with two ovarian cancer cell-line cultures. One line was phenotypically epithelial while the other mesenchymal. The investigators monitored gene expression profiles of the two OC cell lines using qRT-PCR (quantitative reverse transcription polymerase chain reaction). The mesenchymal cell line cultures were treated with the miRNA, miR-429, which had been implicated in EMT in other cancers. The effect of over-expression of miR-429 in the metastatic OC cells was monitored on molecular (qRT-PCR and microarray) and functional (morphology, migration, invasiveness, and anchorage independence assays) levels.

Results revealed that overexpression of miR-429 in mesenchymal-like OC cells resulted in reversal of the mesenchymal phenotype (mesenchymal–epithelial transition, MET).

"We found that when we introduced miR-429 into the highly metastatic ovarian cancer cells, they became less invasive, less migratory and more like the cancer cells associated with primary tumors,” said Dr. McDonald. "We are hopeful that we have found an effective way to drive metastasizing ovarian cancer cells back to their primary cancer stage where they can be more effectively treated with existing chemotherapies.”

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Georgia Institute of Technology