{"id":12119,"date":"2017-01-19T00:00:41","date_gmt":"2017-01-19T08:00:41","guid":{"rendered":"https:\/\/vermont.salk.edu\/?post_type=disclosure&p=12119"},"modified":"2024-01-30T15:35:25","modified_gmt":"2024-01-30T23:35:25","slug":"pancreatic-tumors-rely-signals-surrounding-cells","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/de\/news-release\/pancreatic-tumors-rely-signals-surrounding-cells\/","title":{"rendered":"Pancreatic tumors rely on signals from surrounding cells"},"content":{"rendered":"
Tumor cells stained with a marker for cancer (green) appear near stromal cells (red).<\/p>\n

Klicken Sie hier<\/a> for a high-resolution image <\/p>\n

Kredit: Salk Institut<\/figcaption><\/figure>\n

LA JOLLA\u2014Just as an invasive weed might need nutrient-rich soil and water to grow, many cancers<\/a> rely on the right surroundings in the body to thrive. A tumor\u2019s microenvironment\u2014the nearby tissues, immune cells, blood vessels and extracellular matrix\u2014has long been known to play a role in the tumor\u2019s growth.<\/p>\n

Now, Salk scientists have pinned down how signals from this microenvironment encourage pancreatic tumors to grow by altering their metabolism. Blocking the pathways involved, they reported in Verhandlungen der Nationalen Akademie der Wissenschaften<\/em><\/a> the week of January 16, 2017, can slow the growth of a pancreatic cancer.<\/p>\n

\u201cPancreatic cancer is a deadly disease and is very understudied when it comes to how it communicates with the microenvironment,\u201d says senior author Ronald Evans<\/a>, director of Salk\u2019s Gene Expression Laboratory, a Howard Hughes Medical Institute<\/a> investigator and holder of the March of Dimes Chair in Molecular and Developmental Biology. \u201cOur findings open up a lot of avenues for future study.\u201d<\/p>\n

Pancreatic cancer has the worst five-year survival rate of any major cancer and is expected to be the second leading cause of cancer deaths by the year 2030. It\u2019s notoriously resistant to both chemotherapies and emerging immunotherapies, Evans says, emphasizing the importance of new treatment paradigms.<\/p>\n

A marker for cancer (green) appears near stomal cells (red) in tumor cells.<\/p>\n

Klicken Sie hier<\/a> for a high-resolution image <\/p>\n

Kredit: Salk Institut<\/figcaption><\/figure>\n

Previous research has shown that the signals coming from surrounding stromal cells include both supportive signals\u2014which help pancreatic tumors grow\u2014and suppressive signals\u2014which try to fight the cancer. To understand specifically how pancreatic cancer cells take advantage of any supportive signals, Evans\u2019s team first had to come up with a method to mimic how pancreatic cancer cells grow so closely integrated with the stroma.<\/p>\n

\u201cWe worked out a culture system so that we could grow human pancreatic cells in a three-dimensional system in both the presence and absence of stromal signals,\u201d says first author Mara Sherman, a former Salk postdoctoral research fellow now at Oregon Health & Science University<\/a>.<\/p>\n

When stromal signaling molecules\u2014isolated from patients or generated in the lab\u2014were present, the metabolism of pancreatic cancer cells changed, the researchers found. Not only were levels of metabolic compounds different, but the expression of certain genes involved in metabolism was turned up, and the epigenome of the cells\u2014molecular markers on DNA that change gene expression on a broader scale\u2014was altered.<\/p>\n

\u201cThe tumor is essentially hacking into that stromal microenvironment and grabbing what it needs to up its metabolism,\u201d says Michael Downes, a Salk senior scientist involved in the research.<\/p>\n

From left: Ronald Evans, Mara Sherman, Ruth Yu, Ann Atkins, Tiffany Tseng and Michael Downes<\/p>\n

Klicken Sie hier<\/a> for a high-resolution image <\/p>\n

Kredit: Salk Institut<\/figcaption><\/figure>\n

To try to block this \u201chacking\u201d of the microenvironment by the cancer cells, the team turned to a drug called JQ1, which is known to block the epigenome changes that they\u2019d observed. Indeed, when JQ1 was added to the 3D culture system, it reversed the genetic changes to the pancreatic cancer cells that the stromal signals had caused. Moreover, when mice with pancreatic tumors were treated with JQ1, tumor growth was slowed.<\/p>\n

More work is needed to reveal whether JQ1, or similar compounds, can shrink or slow the growth of pancreatic tumors in humans and what other pathways in the cancer cells may be responding to the tumor microenvironment, but the findings pave the way for that research.<\/p>\n

Other researchers on the study were Ruth T. Yu, Tiffany W. Tseng, Sihao Liu, Morgan Truitt, Nanhai He, Ning Ding, Annette Atkins, and Mathias Leblanc of the Salk Institute; Cristovao Sousa of Harvard Medical School<\/a>; Christopher Liddle of the University of Sydney<\/a>; Eric Collisson of the University of California, San Francisco<\/a>; John Asara of Beth Israel Deaconess Medical Center<\/a>; and Alec Kimmelman of the Dana-Farmer Cancer Institute<\/a>.<\/p>\n

The work and the researchers involved were supported by grants from the National Institutes of Health, the Glenn Stiftung f\u00fcr medizinische Forschung<\/a>, der Die gemeinn\u00fctzige Stiftung von Leona M. und Harry B. Helmsley<\/a>, and Ipsen\/Biomeasure<\/a>.<\/p>","protected":false},"featured_media":12116,"template":"","faculty":[91],"disease-research":[46,172],"class_list":["post-12119","disclosure","type-disclosure","status-publish","has-post-thumbnail","hentry","faculty-ronald-evans","disease-research-cancer-biology","disease-research-pancreatic-cancer"],"acf":[],"yoast_head":"\nPancreatic tumors rely on signals from surrounding cells - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/de\/news-release\/pancreatic-tumors-rely-signals-surrounding-cells\/\" \/>\n<meta property=\"og:locale\" content=\"de_DE\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Pancreatic tumors rely on signals from surrounding cells - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"Tumor cells stained with a marker for cancer (green) appear near stromal cells (red).\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.salk.edu\/de\/news-release\/pancreatic-tumors-rely-signals-surrounding-cells\/\" \/>\n<meta property=\"og:site_name\" content=\"Salk Institute for Biological Studies\" \/>\n<meta property=\"article:modified_time\" content=\"2024-01-30T23:35:25+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2017\/01\/889-1.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"512\" \/>\n\t<meta property=\"og:image:height\" content=\"512\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data1\" content=\"4 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/pancreatic-tumors-rely-signals-surrounding-cells\\\/\",\"url\":\"https:\\\/\\\/www.salk.edu\\\/news-release\\\/pancreatic-tumors-rely-signals-surrounding-cells\\\/\",\"name\":\"Pancreatic tumors rely on signals from surrounding cells - 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Shermana, Ruth T. Yua, Tiffany W. Tsenga, Cristovao M. Sousab, Sihao Liua, Morgan L. Truitta, Nanhai Hea, Ning Dinga, Christopher Liddlec, Annette R. Atkinsa, Mathias Leblanca, Eric A. Collissond, John M. Asarae, Alec C. Kimmelmanb, Michael Downesa, Ronald M. Evans","paper_title":"Stromal cues regulate the pancreatic cancer epigenome and metabolome","subhead":"Salk scientists find that targeting the interaction between a pancreatic tumor and its microenvironment could weaken cancer","home_photo":"","listing_photo":"","legacy_boilerplate":[],"hide_boilerplate":[],"disable_date":false,"listing_excerpt":"<p>LA JOLLA\u2014Just as an invasive weed might need nutrient-rich soil and water to grow, many <a href=\"https:\/\/www.salk.edu\/science\/research\/cancer-biology\/\">cancers<\/a> rely on the right surroundings in the body to thrive. A tumor\u2019s microenvironment\u2014the nearby tissues, immune cells, blood vessels and extracellular matrix\u2014has long been known to play a role in the tumor\u2019s growth.<\/p>\n","descriptive_blurb":"","has_journal_cover":false,"poster_quote":"","doi":"","og_image_override":false},"_links":{"self":[{"href":"https:\/\/www.salk.edu\/de\/wp-json\/wp\/v2\/disclosure\/12119","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.salk.edu\/de\/wp-json\/wp\/v2\/disclosure"}],"about":[{"href":"https:\/\/www.salk.edu\/de\/wp-json\/wp\/v2\/types\/disclosure"}],"version-history":[{"count":5,"href":"https:\/\/www.salk.edu\/de\/wp-json\/wp\/v2\/disclosure\/12119\/revisions"}],"predecessor-version":[{"id":47088,"href":"https:\/\/www.salk.edu\/de\/wp-json\/wp\/v2\/disclosure\/12119\/revisions\/47088"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.salk.edu\/de\/wp-json\/wp\/v2\/media\/12116"}],"wp:attachment":[{"href":"https:\/\/www.salk.edu\/de\/wp-json\/wp\/v2\/media?parent=12119"}],"wp:term":[{"taxonomy":"faculty","embeddable":true,"href":"https:\/\/www.salk.edu\/de\/wp-json\/wp\/v2\/faculty?post=12119"},{"taxonomy":"disease-research","embeddable":true,"href":"https:\/\/www.salk.edu\/de\/wp-json\/wp\/v2\/disease-research?post=12119"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}