According to the current understanding, cancer develops when a single, aberrant cell proliferates into a full-fledged tumor. However, new evidence suggests that cancer cells can also transform healthy cells into tumorous ones via an “oncogenic field effect.” This research could lead to a more complete understanding of the spread of cancer and to better cancer detection methods (1).
[While many types of cells, including neurons and stem cells, secrete exosomes (membrane-bound vesicles associated with cell-to-cell communication and cell waste management), scientists have recently discovered that cancerous cells in particular produce many more exosomes than noncancerous cells (1).]
Taking this information, Raghu Kalluri and his colleagues at the University of Texas MD Anderson Cancer Center further determined that cancerous exosomes contain pre-miRNAs and several RISC-loading complex proteins like AGO2, TRBP, and Dicer not present in normal cell exosomes. These components can induce a normal cell to turn tumorous (1).
Pre-miRNAs interact with RISC-loading complex proteins to produce mature miRNAs, endogenous sequences of 18 to 24 nucleotides, that regulate gene expression on a post-transcriptional level by upregulating or downregulating mRNA transcribed from DNA (1).
Based on a series of experiments using metastatic and nonmetastatic human breast cancer cells and serum, the scientists studied the mechanism that cancerous exosomes may use to produce this “oncogenic field effect” (1).
While normal cells incubated with cancerous exosomes normally turned tumorous, the addition of Dicer antibodies reduced tumor growth, suggesting that miRNA regulation of oncogenic genes is Dicer-dependent (1).
When healthy female mice were treated with exosomes generated by human breast cancer cells co-injected with noncancerous epithelial human cells (MCF10A), researchers found an increase in miRNAs and formation of tumors by the MCF10A cells. Noncancerous human epithelial cells injected into mice did not induce tumor growth (1).
Besides breast cancer, other cancer cells also produce exosomes that contain pre-miRNA and RISC-complex loading proteins. These components were detected in the serum taken from patients suffering from ovarian, breast, and endometrial cancers, but not in serum from healthy subjects (1).
Based on these findings, scientists believe that presence of exosomes and Dicer in these exosomes may serve as more-readily detectable biomarkers for cancer than currently existing methods, which include detecting lone tumor cells in the bloodstream during metastasis (1,2).
Kalluri and his colleagues also acknowledge the need for more research due to the complex in vivo environment of the human body. However, their research suggests a new understanding of exosomes in cancer (1,2).
“It’s amazing,” said Khalid Al-Nedawi, Ph.D., an assistant professor and cancer researcher at McMaster University in Nature. “These vesicles were considered garbage cans. This paper really brings us closer to harnessing the potential of these tiny vesicles” (2).
Sources:
1. Melo, S.A., Sugimoto, H., O’Connell, J.T., Kato, N., Villanueva, A., Vidal, A., …, Kalluri, R. (2014, October 23). Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis. Cancer Cell. doi: 10.1016/j.ccell.2014.09.005
2. Ledford, H. (2014, October 23). Cancer cells can ‘infect’ normal neighbours. Nature. Retrieved from www.nature.com