Authors: Lauren Pulling
Researchers have identified a key protein essential for tumor formation in one of the deadliest forms of brain cancer, glioblastoma. Glioblastoma is resistant to chemotherapy and radiation therapy and is difficult to treat with surgery. The finding that the protein, termed Oncostatin M Receptor (OSMR), regulates tumor formation may help in the search for potential new treatments for the cancer.
The study, published recently in Nature Neuroscience, is the first to identify the role of OSMR in glioblastoma. It reports that the protein is a cytokine coreceptor involved in the EGFRvII–STAT3 signaling pathway, which has previously been identified as crucial for tumor formation in glioblastoma.
The research team, led by Arezu Jahani-Asl (Harvard Medical School, MA, USA), studied tumor stem cells from glioblastoma patients and indicated that, contrary to previous belief, only a select number of cell types are capable of reproducing to form a full tumor. If only one of these cell types is present however, for example after surgery, it is capable of forming a full tumor.
The researchers demonstrated that blocking OSMR activity in these cells in mice significantly suppresses cell proliferation and tumor formation.
Michael Rudnicki, senior author, commented: “Being able to stop tumor formation entirely was a dramatic and stunning result. It means that this protein is a key piece of the puzzle, and could be a possible target for future treatments.”
Further study of the role of OSMR indicated that higher OSMR expression in human glioblastoma tumor samples correlated with faster patient decline and death. Similarly, mice injected with human glioblastoma stem cells with low OSMR expression survived for 30% longer than those injected with stem cells with normal OSMR expression levels.
Rudnicki and his team also discovered that EGFRvII binds with the coreceptor OSMR in order to activate a feed-forward signaling mechanism with STAT3 to promote cell proliferation and tumor growth. It is hoped that the identification of OSMR as a coreceptor for EGFRvIII will lead to new successful treatment developments that target the EGFRvII–STAT3 pathway.
“This study raises the exciting prospect of potential new targets for a lethal disease,” commented Azad Bonni, senior co-author. “The next step is to find small molecules or antibodies that can shut down the protein OSMR or stop it from interacting with EGFR. But any human treatment targeting this protein is years away.”
Sources: Jahani-Asl A, Yin H, Soleimani V et al. Control of glioblastoma tumorigenesis by feed forward cytokine signaling. Nat Neurosci. doi:10.1038/nn.4295 (2016) (Epub ahead of print); Ottawa Hospital press release