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Tumor cells share oncogenic receptors

Microvesicles (bright dots) containing mutant receptor are shed by glioma cells. RAK/MACMILLAN

Mutant receptors made in one tumor cell can be passed to tumor cells lacking them, say Khalid Al-Nedawi, Janusz Rak (McGill University, Montreal), and colleagues, increasing oncogenicity of the entire tumor.

In a certain type of human brain cancer called glioma, the gene encoding epidermal growth factor receptor is often mutated, creating a version of the receptor that is truncated and overactive. The presence of this mutant version, called EGFRvIII, can signify a more aggressive disease state, even if many cells in the tumor don't express the receptor gene. Expressing and nonexpressing cells both display the mutant protein, however, and both contribute to malignancy. "It was hard to understand how receptor expression in one small set of cells could upgrade the entire tumor" to the more aggressive form, Rak says.

The authors found that glioma cells expressing EGFRvIII transferred this errant receptor to nonexpressing cells via microvesicles—small plasma membrane buds. The microvesicles were produced in abundance by the mutant expressing cells and were widely taken up by receptor-negative cells. Within 24 hours, these recipient cells had increased receptor-triggered downstream signaling and, compared with cells without receptors, could form twice as many colonies in agar—a standard sign of increased malignancy.

"We propose there is a much greater level of communication between cancer cells than is usually appreciated," Rak says. Microvesicles aren't just shared among cells; previous work has shown that they're also shed into the bloodstream. The finding that glioma cells are sending out microvesicles could therefore potentially lead to a less invasive means of brain tumor characterization.

Al-Nedawi, K., et al. 2008. Nat. Cell Biol. doi:10.1038/ncb1725.[CrossRef][Medline]

Richard Robinson

rrobinson{at}nasw.org

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This Article Full Text (PDF, 891K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Robinson, R. Search for Related Content PubMed Articles by Robinson, R. Social Bookmarking                            What's this?