Protein Mediating Melanoma Tumor Metastasis Identified

The interaction between melanoma cells and surrounding endothelial tissue that is required for the cancer to spread is mediated, at least in part, by the protein encoded by the neuropilin-2 (NRP2) gene.

Metastasis causes more than 90% of solid tumor deaths throughout the world and it is a particularly aggressive factor in melanoma. While it was understood that this aggressive behavior depended on tumor-stromal interaction, the molecular mechanisms involved had not been elucidated.

To study this interaction investigators at Boston University (MA, USA) and Johns Hopkins University (Baltimore, MD, USA) developed a novel screening method based on co-culture methodology that allowed simultaneous tracking of genomic and phenotypic changes in interacting tumor and endothelial cells in vitro.

Results published in the February 15, 2011, online edition of the journal Cancer Research revealed a dramatic rearrangement of endothelial cell networks into patterns reminiscent of vascular beds, even on plastic and glass surfaces. Multiple genes were upregulated in the process, many coding for cell surface and secreted proteins, including neuropilin-2 (NRP2).

"We found that neuropilin is an important mediator of melanoma cell and blood vessel cell interactions,” said senior author Dr. Rhoda Alani, professor of dermatology at Boston University. "We can now investigate this molecule as a potential biomarker and melanoma treatment target. We can also use the unique methodology developed in these studies to evaluate cellular crosstalk between other tumor cell types and vessel cells. Such studies are likely to provide important insights into the metastatic process for other cancers.”

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Boston University
Johns Hopkins University