Featured Research

from universities, journals, and other organizations

Probing how pancreatic cancers metastasize

Date:
March 25, 2013
Source:
University of North Carolina School of Medicine
Summary:
Researchers have discovered that a protein found in the cells surrounding pancreatic cancers play a role in the spread of the disease to other parts of the body.

Dot-like invadopodia assemble into circular groups known as “rosettes” inside cancer-associated fibroblasts (CAFs) grown from a human pancreas tumor. CAFs utilize palladin-containing invadopodia to help the cancer cells move across tissue boundaries.
Credit: Image courtesy of University of North Carolina School of Medicine

Researchers at the University of North Carolina at Chapel Hill have discovered that a protein found in the cells surrounding pancreatic cancers play a role in the spread of the disease to other parts of the body.

In a finding to be published in the March 25 issue of Oncogene, researchers in the lab of Carol Otey, PhD, found that the protein palladin enhances the ability of cancer-associated fibroblasts (CAFs) to assemble organelles known as invadopodia to break down the barriers between cells and create pathways for tumors to spread throughout the body. Otey is a professor in the Department of Cell Biology and Physiology and a member of UNC Lineberger Comprehensive Cancer Center.

"There's a growing body of literature that shows that these cells have a role in cancer formation and metastasis," said Otey.

Using both enzymatic action and physical force, the invadopodia create channels for tumor cells to migrate from their point of origin to other organs. Otey said that researchers, using cultured cancer cells suspended between layers of collagen, have been able to observe CAFs tunneling through the collagen layer and record cancer cells migrating through those channels.

In previous studies, researchers in the Otey lab and other labs have shown that CAFs surrounding pancreatic tumors express high levels of palladin. In healthy tissue, fibroblasts are the most common type of connective tissue found in mammals. In cancerous cells, CAFs are the most numerous cells found in the tumor microenvironment.

Researchers have begun focusing significant attention to the tumor microenvironment, as evidence grows that the cells and proteins found outside of cancer cells play a crucial role in tumor formation, growth and metastasis. Understanding the interplay between the microenvironment and the tumors could lead to new targets for treatment and screening, especially in cancers that are resistant to therapies that directly target the cancerous cells.

"Cells seem to be partnering together to form the tumor and promote its growth," said Otey.

Using pharmacological inhibitors and gene-silencing approaches, Otey and the research team discovered that disrupting palladin in CAFs reduced the ability of the cells to form invadopodia. Increasing the level of palladin in CAFs, by contrast, increased the rate of growth and metastasis of tumors in mouse models. Their results indicate that palladin may be part of a molecular pathway that includes two additional molecules, protein kinase C and Cdc42.

"These results demonstrate that the behavior of CAFs plays a very important role in modulating the behavior of tumor cells, and also point to a specific molecular pathway that could be a useful drug target for inhibiting tumor progression," said Otey.

Since Otey discovered palladin more than a decade ago, researchers in her lab have examined the protein's role in both healthy and cancerous cells. Citing her own work, research from the Brentnall lab at University of Washington, and corroborating work such as a study from the Cukierman lab at Temple University's Fox Chase Cancer Center that found high levels of the palladin protein correlated strongly with low survival rates in renal carcinoma patients, Otey said that the evidence points toward a strong correlation between palladin expression in CAFs and the aggressiveness of tumor progression.

In future research, Otey plans to examine the levels of palladin in other types of cancer. As the Fox Chase study suggests, the mechanisms that she and her collaborators have discovered may play a role in cancers other than pancreatic.

"Knowing more about this may give us better tools to slow down metastasis," said Otey.

Study co-authors from UNC include first author Silvia M. Goicoechea, Rafael Garcνa-Mata, Judy Staub, Alejandra Valdivia, Lisa Sharek, Jen Jen Yeh and Hong Jin Kim. Other study co-authors are Chris McCulloch from University of Toronto, Canada; Rosa Hwang from University of Texas M.D. Anderson Cancer Center, Houston, TX; and Raul Urrutia from Mayo Clinic College of Medicine, Rochester, Minn.

This study was supported by grants from the NIH (GM081505), the NSF, the Elsa U. Pardee Foundation and the UNC University Cancer Research Fund.


Story Source:

The above story is based on materials provided by University of North Carolina School of Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. S M Goicoechea, R Garcνa-Mata, J Staub, A Valdivia, L Sharek, C G McCulloch, R F Hwang, R Urrutia, J J Yeh, H J Kim, C A Otey. Palladin promotes invasion of pancreatic cancer cells by enhancing invadopodia formation in cancer-associated fibroblasts. Oncogene, 2013; DOI: 10.1038/onc.2013.68

Cite This Page:

University of North Carolina School of Medicine. "Probing how pancreatic cancers metastasize." ScienceDaily. ScienceDaily, 25 March 2013. <www.sciencedaily.com/releases/2013/03/130325101418.htm>.
University of North Carolina School of Medicine. (2013, March 25). Probing how pancreatic cancers metastasize. ScienceDaily. Retrieved September 20, 2014 from www.sciencedaily.com/releases/2013/03/130325101418.htm
University of North Carolina School of Medicine. "Probing how pancreatic cancers metastasize." ScienceDaily. www.sciencedaily.com/releases/2013/03/130325101418.htm (accessed September 20, 2014).

Share This



More Health & Medicine News

Saturday, September 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Could Grief Affect The Immune Systems Of Senior Citizens?

Could Grief Affect The Immune Systems Of Senior Citizens?

Newsy (Sep. 19, 2014) — The study found elderly people are much more likely to become susceptible to infection than younger adults going though a similar situation. Video provided by Newsy
Powered by NewsLook.com
Jury Delivers Verdict in Salmonella Trial

Jury Delivers Verdict in Salmonella Trial

AP (Sep. 19, 2014) — A federal jury has convicted three people in connection with an outbreak of salmonella poisoning five years ago that sickened hundreds of people and was linked to a number of deaths. (Sept. 19) Video provided by AP
Powered by NewsLook.com
How The 'Angelina Jolie Effect' Increased Cancer Screenings

How The 'Angelina Jolie Effect' Increased Cancer Screenings

Newsy (Sep. 19, 2014) — Angelina's Jolie's decision to undergo a preventative mastectomy in 2013 inspired many women to seek early screenings for the disease. Video provided by Newsy
Powered by NewsLook.com
The Cost of Ebola

The Cost of Ebola

Reuters - Business Video Online (Sep. 18, 2014) — As Sierra Leone prepares for a three-day "lockdown" in its latest bid to stem the spread of Ebola, Ciara Lee looks at the financial implications of fighting the largest ever outbreak of the disease. Video provided by Reuters
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins