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<h2 class="element-invisible">You are here</h2><div class="breadcrumb"><a href="/">Home</a> » <a href="/news-events">News & Events</a> » <a href="/news-events/nih-research-matters">NIH Research Matters</a></div> <div class="l-region l-region--section-header">
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<p class="publishdate"><span property="dc:date" datatype="xsd:dateTime" content="2020-02-25T00:00:00-05:00" class="date-display-single">February 25, 2020</span></p><div class='syndicate'><h1>Neurons play role in oral cancer </h1><div class="callout callout-with-border"><h3>At a Glance</h3>
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<ul>
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<li>Scientists discovered a new role for nerves in oral cancer progression, in which tumor cells send genetic messages that transform nerves into cancer-promoting agents.</li>
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<li>Targeting this nerve-tumor crosstalk could lead to more effective treatments for people with head and neck cancers.</li>
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</ul></div><div class="media-float-right"><div class="ds-1col file file-image file-image-jpeg view-mode-floated_media clearfix">
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<picture title="Neurons growing neurites">
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<!--[if IE 9]><video style="display: none;"><![endif]-->
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-large/public/news-events/research-matters/2020/20200225-exosomes.jpg?itok=sgLcZQZ1&timestamp=1582565684 1x" media="screen and (min-width: 960px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2020/20200225-exosomes.jpg?itok=yUq79NWP&timestamp=1582565684 1x" media="screen and (min-width: 800px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium-small/public/news-events/research-matters/2020/20200225-exosomes.jpg?itok=Dp32Mtxq&timestamp=1582565684 1x" media="screen and (min-width: 600px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-small/public/news-events/research-matters/2020/20200225-exosomes.jpg?itok=RMcPnPus&timestamp=1582565684 1x" media="screen and (min-width: 480px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-tiny/public/news-events/research-matters/2020/20200225-exosomes.jpg?itok=K84hwz5d&timestamp=1582565684 1x" media="screen and (min-width: 0)" />
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<!--[if IE 9]></video><![endif]-->
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<img src="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2020/20200225-exosomes.jpg?itok=yUq79NWP&timestamp=1582565684" alt="Neurons growing neurites" title="Neurons growing neurites" />
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||
</picture><span class="caption">Mouse sensory neurons sprout projections called neurites (red) after receiving growth signals from nearby oral cancer cells. </span><span class="credit">Moran Amit, MD Anderson Cancer Center</span></div>
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||
</div><p>More than 53,000 Americans this year are predicted to be diagnosed with head and neck cancers, some of which arise in the oral cavity. Advanced stages of the disease are hard to treat. Effective therapies must target both the tumor and its microenvironment—the supportive network of connective tissue, blood vessels, cells, and molecules that surround the tumor.</p>
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||
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||
<p>Nerves infiltrate this cancerous environment early in tumor development. Recent studies suggest that these nerves play a role in tumor growth and progression. Scientists are trying to understand the tumor-nerve relationship in hope that it could lead to better therapies for head and neck cancer.</p>
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||
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<p>A research team led by Drs. Moran Amit, George A. Calin, and Jeffrey N. Myers from the University of Texas MD Anderson Cancer Center began their study into this relationship by analyzing human data from the Cancer Genome Atlas. Their work was funded in part by NIH’s National Institute of Dental and Craniofacial Research (NIDCR) and other NIH components. The findings were published on February 20, 2020, in <em>Nature</em>.</p>
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||
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||
<p>The team found that high nerve density and <em>TP53</em> mutations in oral cancer tissue were associated with earlier death. <em>TP53 </em>is the most commonly mutated gene in head and neck cancer. Its protein product, p53, is a tumor suppressor that acts as a brake on cancer growth. This function is lost when the gene is mutated, enabling tumors to grow unrestrained.</p>
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||
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||
<p>Using mouse models of oral cancer and laboratory cell cultures, the scientists confirmed the connection between p53 and nerve density. Sensory neurons (a type of nerve cell) in culture that were exposed to p53-deficient oral cancer cells sprouted projections called neurites. Sensory nerves are highly abundant in the oral cavity and convey touch, texture, and taste. These results suggest that loss of p53 in oral cancer enhances nerve growth and density in the tumor microenvironment.</p>
|
||
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||
<p>Further experiments showed that growth cues come from tumors to neurons in the form of signaling molecules called microRNAs. These tiny snippets of RNA can alter growth, identity, and other functions of targeted cells. The scientists found that spherical delivery vehicles called extracellular vesicles were transferring the microRNAs from tumors to nerve cells in the microenvironment. These microRNAs nudge sensory neurons to reduce their normal gene activity and adopt genetic characteristics of a different class of nerve cells, known as adrenergic neurons, that are usually rare in the oral cavity.</p>
|
||
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||
<p>Signals from adrenergic nerves trigger the body’s “fight-or-flight” response. Past studies showed that these signals can also promote tumor progression in other cancers. To confirm that the adrenergic neurons were promoting tumors, the scientists blunted adrenergic signaling in mice—either by disabling sensory nerves or giving adrenergic-blocking drugs. The resulting tumors were slower growing, smaller, and surrounded by fewer adrenergic-like neurons.</p>
|
||
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<p>“We wanted to understand the reciprocal tumor-nerve signals that drive cancer progression,” Amit says. “This information could help scientists develop the means to target this crosstalk.”</p>
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<p>—by Catherine Evans, Ph.D.</p></div><h2 class="label-above">Related Links</h2><ul class="spaced print-urls"><li><a href="https://www.nih.gov/news-events/nih-research-matters/blocking-dna-repair-restores-sensitivity-brain-tumors-treatment-mice" target="_top">Blocking DNA Repair Restores Sensitivity of Brain Tumors to Treatment in Mice</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/how-elephants-defend-against-cancer" target="_top">How Elephants Defend Against Cancer</a></li><li><a href="https://www.nidcr.nih.gov/news-events/nidcr-news/how-build-cancer" target="_top">How to Build a Cancer</a></li><li><a href="https://www.cancer.gov/types/head-and-neck" target="_top">Head and Neck Cancer</a></li><li><a href="https://www.nidcr.nih.gov/health-info/oral-cancer" target="_top">Oral Cancer</a></li></ul><p class="footnote"><strong class="label-inline">References: </strong><a href="https://www.ncbi.nlm.nih.gov/pubmed/32051587">Loss of p53 drives neuron reprogramming in head and neck cancer.</a> Amit M, Takahashi H, Dragomir MP, Lindemann A, Gleber-Netto FO, Pickering CR, Anfossi S, Osman AA, Cai Y, Wang R, Knutsen E, Shimizu M, Ivan C, Rao X, Wang J, Silverman DA, Tam S, Zhao M, Caulin C, Zinger A, Tasciotti E, Dougherty PM, El-Naggar A, Calin GA, Myers JN. <em>Nature</em>. 2020 Feb 12. doi: 10.1038/s41586-020-1996-3. [Epub ahead of print]. PMID: 32051587.</p><p class="footnote"><strong class="label-inline">Funding: </strong>NIH’s National Institute of Dental and Craniofacial Research (NIDCR), National Center for Advancing Translational Sciences (NCATS), NIH Common Fund, National Cancer Institute (NCI), and National Institute of General Medical Sciences (NIGMS); US Department of Defense; MD Anderson Cancer Moonshots Program; MD Anderson Sister Institution Network Fund; Estate of C. G. Johnson Jr.; Thompson Family Foundation Initiative; S.I.A. funds; National Natural Science Foundation of China.</p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/research-context-can-we-slow-aging">Research in Context: Can we slow aging?</a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/brain-changes-observed-during-pregnancy">Brain changes observed during pregnancy</a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/risk-future-burden-dementia-united-states">Risk and future burden of dementia in the United States </a></p>
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<p><a href="https://www.nih.gov/news-events/nih-research-matters/complete-wiring-map-adult-fruit-fly-brain">Complete wiring map of an adult fruit fly brain</a></p>
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<p><strong>Editor:</strong> Harrison Wein, Ph.D.</p>
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<p><strong>Assistant Editors:</strong> Vicki Contie and Brian Doctrow, Ph.D.</p>
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<p><strong><em>NIH Research Matters </em></strong>is a weekly update of NIH research highlights reviewed by NIH’s experts. It's published by the <a href="/institutes-nih/nih-office-director/office-communications-public-liaison">Office of Communications and Public Liaison</a> in the <a href="/institutes-nih/nih-office-director">NIH Office of the Director</a>.</p>
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