Last month, MesotheliomaHelp reported on early research from the UK where resea
rchers identified the Spns2 gene could reduce metastasis in lung cancer, and, potentially, in mesothelioma. Identifying a gene or protein effective in halting metastasis is a hot research topic, and now, another team of researchers report they have taken a closer look at a two-part protein to assess its ability to slow cancer growth.
Researchers from the Medical University of South Carolina (http://academicdepartments.musc.edu/newscenter/2016/wrangle-rubinstein-lung-cancer.html) knew that the NRP genes, NRP1 and NRP2, are up-regulated in cancer tumors leading to poor patient prognosis. However, the NRP2 protein is comprised of a 2a and 2b isoform, and when the scientists delved deeper into the effects on lung cancer, they found that while the two are “nearly identical” the differences were significant enough to affect cancer progression.
“Whenever we expressed NRP2b the cancer metastasized, and whenever we expressed NRP2a progression and metastasis were suppressed,” said Robert Gemmill, Ph.D. who holds the Melvyn Berlinsky Endowed Chair for Cancer Research at MUSC. “Clearly, with the 2b isoform, we have found something that promotes metastasis.”
Lung cancer and pleural mesothelioma, the signature cancer of asbestos, are both aggressive and both quickly metastasize, limiting survival. Past research has shown that it is this metastasis, not the original cancer tumors, that leads to death in nearly 90 percent of cancer patients. Unlocking the mystery of metastasis is critical for helping patients lead a longer life.
Through various experiments, the MUSC team found that the potent tumor suppressor, SEMA3F, was reduced or lost, while NRP2b was induced, leading to lung cancer progression. They then found that when NRP2b was knocked out, or suppressed, and NRP2a was induced, chemotherapy resistance was limited, and metastasis was limited.
These findings were encouraging to the team and they hope the findings will “open new avenues for potential therapies,” and that other scientists will pick up the research for development of new treatments for lung cancer. Gemmill points out that uncovering the effects of NRP2b could lead to monoclonal antibodies to target the 2b isoform, new immunotherapies, and possibly using NRP2b as a biomarker for predicting patients’ responses to treatment.
“I think a lot of people are going to sit up when they read this article and say, ‘I wonder what it does in my system?'” said Gemmill.
Nearly 3,000 Americans are diagnosed with mesothelioma each year. The cancer is terminal, and the prognosis is often less than 18 months.
Read the full study in the Jan. 17 issue of Science Signaling (http://stke.sciencemag.org/content/9/450/rs12).