Navigation Links
Potential treatment target identified in an animal model of pancreatic cancer
Date:7/1/2012

Detailed analysis of genes expressed in circulating tumor cells (CTCs) -- cells that break off from solid tumors and travel through the bloodstream -- has identified a potential treatment target in metastatic pancreatic cancer. In a report that will appear in Nature and has received advance online publication, Massachusetts General Hospital (MGH) Cancer Center investigators describe finding increased expression of WNT2, a member of a known family of oncogenes, in CTCs from a mouse model of the deadly tumor and from human patients. The researchers were able to capture the CTCs - present in the bloodstream at extremely low levels - using a microchip-based device previously developed by members of the team.

"This proof of principle study is the first to show that, by studying both mouse and human pancreatic cancer cells captured with this device, we can dissect genes that are overexpressed in these cells and identify signaling pathways that allow them to survive in the bloodstream," says Daniel Haber, MD, PhD, director of the MGH Cancer Center and senior author of the Nature paper. "We also found that targeting a key step in these pathways can reduce metastatic potential, which is critically important for control of pancreatic cancer. This study would not have been possible without a way to isolate rare CTCs from both mouse models and human patients."

Using the second-generation version of the CTC-chip, developed in collaboration with the MGH Center for Engineering in Medicine, the researchers first captured CTCs from mice genetically programmed to develop pancreatic cancer, one of the most deadly tumors since it is rarely diagnosed before spreading. Analysis of RNA expression levels in pancreatic CTCs, in primary tumor cells, and in normal pancreatic tissue identified several genes with significantly increased expression in the CTCs. One of these, WNT2, belongs to a family of developmental genes often overexpressed in cancer, and while the gene's expression in pancreatic tumors was higher than in normal tissue, WNT2 expression was significantly more elevated in both CTCs and metastatic cells.

Closer analysis of cells from several individual animals confirmed that WNT2 was highly expressed in pancreatic cancer CTCs and in metastases, but WNT2-expressing cells were found to be rare in primary tumors. Testing the consequences of WNT2 expression indicated that cancer cells expressing the gene were more likely to generate metastases, probably because of an improved ability to survive after dislodging from the primary tumor and entering the bloodstream.

The researchers tested several agents known to inhibit the activity of molecules in the WNT2 pathway their results implied was associated with pancreatic cancer and found that inhibition of TGF-beta activated kinase 1 (TAK1) prevented metastasis-associated activities in cultured CTCs. Knocking down TAK1 expression with RNA interference also reduced the development of metastasis in mice injected with WNT2-expressing CTCs. A significant percentage of tested CTCs from patients with metastatic pancreatic cancer were found to express WNT-related genes, along with other components of the signaling pathway associated with pancreatic cancer in the mouse model.

"The picture in more complicated in humans, since multiple WNTs are upregulated," Haber says. "But the TAK1 inhibitor we tested appears to have an effect on diverse WNT pathways involved in the survival of pancreatic CTCs. We previously reported that TAK1 inhibition has promise for treating a genetically defined subset of colon cancers, and these findings now extend the relevance of the TAK1 pathway to suppression of blood-borne metastasis in pancreatic cancer. Considerable more work will be needed to fully understand the critical pathways involved, but it is our hope that TAK1 inhibitors will ultimately be developed for clinical testing."


'/>"/>

Contact: Sue McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
Source:Eurekalert

Related medicine news :

1. Gene sequencing project identifies potential drug targets in common childhood brain tumor
2. Device implanted in brain has therapeutic potential for Huntingtons disease
3. Bioinformatics experts at the CNIO explore additional coding potential hidden in the human genome
4. Mutations in JAK3 gene identified in subtype of lymphoma provide potential drug target
5. Misuse of over-the-counter pain medication is potential health threat
6. VCU Massey Cancer Center sees potential in novel leukemia treatment
7. Hybrid vaccine demonstrates potential to prevent breast cancer recurrence
8. A closer look at PARP-1 reveals potential new drug targets
9. New study of NIH funding allocations suggests potential efficiency gains
10. UNC study shows potential to revive abandoned cancer drug by nanoparticle drug delivery
11. Army researcher develops potential vaccine carrier
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/18/2017)... ... February 17, 2017 , ... Focused start-ups, not ... the industry, according to the recent NEJM Catalyst Insights Report on the New ... NEJM Catalyst Insights Council, a qualified group of U.S. executives, clinical leaders, and ...
(Date:2/18/2017)... ... February 18, 2017 , ... ProParagraph Fashion Volume 2 features ... ProParagraph Fashion Volume 2 for all multi-line FCPX project needs. Great for ... and choose from hand-crafted trend-setting designs with smooth animations that will add stylistic ...
(Date:2/17/2017)... ... February 17, 2017 , ... The Alliance ... change designed to further positively impact the health and wellness of our community ... considered it our duty to seriously consider releasing our assets beyond our 5% ...
(Date:2/17/2017)... ... February 17, 2017 , ... Empowering ... Francis' goals for each and every seminar, session and class she offers. ... five different brainwave tools which help energize creativity, focus mental functions, enhance athletic ...
(Date:2/17/2017)... WASHINGTON (PRWEB) , ... February 17, 2017 , ... ... communities by fall 2017 season , Trinity Health and the U.S. Soccer Foundation ... for Success program in underserved communities. Soccer for Success, the Foundation’s soccer mentoring ...
Breaking Medicine News(10 mins):
(Date:2/17/2017)... DUBLIN , Feb. 17, 2017 ... ("Theravance Biopharma" or the "Company") today announced the ... novel, potent, and orally administered pan-Janus kinase (JAK) ... 12 th Congress of the European Crohn,s ... the Company reported further data from its completed ...
(Date:2/17/2017)... Research and Markets has announced the addition of the "Drug-Eluting ... ... for the US, Canada , Japan ... Latin America , and Rest of World. Annual estimates and ... historic analysis is provided for these markets. Market data and analytics are ...
(Date:2/17/2017)... LOUIS , Feb. 17, 2017   FormFast ... has announced a new partnership with Engage , ... the United States . FormFast will serve as ... of Engage,s implementations with MEDITECH .  ... provides essential functionality to complement and enhance the electronic ...
Breaking Medicine Technology: