Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Potential treatment target identified in an animal model of pancreatic cancer

Analyzing circulating tumor cells reveals signaling pathway that may be essential to spread of deadly tumor

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."

Haber is the Kurt Isselbacher/Peter Schwartz Professor of Oncology at Harvard Medical School and a Howard Hughes Medical Institute investigator. Co-lead authors of the Nature report are Min Yu, PhD, and David Ting, MD, PhD, MGH Cancer Center. Additional co-authors include Shyamala Maheswaran, PhD, Ben Wittner, PhD, Sridhar Ramaswamy, MD, Nabeel Bardeesy, PhD, and Lecia Sequist, MD, MGH Cancer Center; and Shannon Stott, PhD, and Mehmet Toner, PhD, MGH Center for Engineering in Medicine. The study was supported by grants from Stand Up to Cancer, the Howard Hughes Medical Institute, the National Institute of Biomedical Imaging and Bioengineering, the National Institutes of Health, the Pancreatic Cancer Action Network and the Warshaw Institute for Pancreatic Cancer Research.

Massachusetts General Hospital (, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $750 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine.

Sue McGreevey | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Microbe hunters discover long-sought-after iron-munching microbe
24.10.2016 | Max-Planck-Institut für marine Mikrobiologie

nachricht Seeking balanced networks: how neurons adjust their proteins during homeostatic scaling.
24.10.2016 | Max-Planck-Institut für Hirnforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Seeking balanced networks: how neurons adjust their proteins during homeostatic scaling.

24.10.2016 | Life Sciences

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

More VideoLinks >>>