Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cancer cell collaborators smooth the way for cancer cells to metastasize

14.12.2015

At ASCB 2015: Cancer cell collaborators unmasked

At ASCB 2015, Vanderbilt researchers show how metastasizing tumors use non-cancerous fibroblasts to make a migration highway through surrounding extracellular matrix.


Red labeled JHU12 head and neck carcinoma cells are migrating on CAF-derived extracellular matrix (green). Images were taken every 10 minutes for 3 hours using a confocal microscope.

Credit: Begum Erdogan & Donna Webb, Vanderbilt University

To get moving, metastasizing cancer needs to enlist non-cancerous collaborators. Suspicions about where these secret cancer allies might be lurking have long been directed at the fibroblasts, the cells that secrete and organize the extracellular matrix (ECM), the ground on which surrounding cells can get a grip. Increasing evidence suggests that fibroblasts near growing tumors are actively assisting cancer cells in spreading locally and metastasizing elsewhere.

But exactly how these cancer-associated fibroblasts (CAFs) provide aid to the cancer enemy was not known until a recent discovery by Begum Erdogan and colleagues in Donna Webb's lab at Vanderbilt University--CAFs clear a highway through the ECM for migrating cancer cells. The researchers will present their work at ASCB 2015 in San Diego on Sunday, December 13 and Tuesday, December 15.

The roadway that CAFs arrange is made of parallel fibers of fibronectin (Fn), a major protein in the ECM mix secreted by all fibroblasts. The Vanderbilt researchers observed CAFs rearranging Fn into parallel bundles instead of the dense mesh that normal tissue fibroblasts (NAFs) make. Taking cancer cells grown from prostate as well as head and neck tumors, the researchers plated them on ECM from CAFs and NAFs. The cancer cells on the CAF matrix were better at moving in a single direction.

But why? CAFs rearrange the matrix into a road because they get a better grip on Fn fibers, the researchers discovered. Using traction force microscopy, they were able to measure the difference. CAFs were stronger than NAFs because they were better at delivering force from the motor protein, myosin II, through connectors called integrins to Fn fibers.

CAFs had higher levels of a Fn-binding integrin plus a switched-on GTPase called Rac, which is critical to cell movement. Inhibiting myosin-II activity with a drug deprived CAFs of their super traction powers and the ECM reverted to its normal disorder. These results solve a longstanding puzzle about cancer metastasis and point to the matrix as a possible target for drugs to stop cancer in its tracks.

###

Cancer-associated fibroblasts promote directional migration of cancer cells via parallel organization of the fibronectin matrix
B. Erdogan1, M. Ao1, B.M. Brewer2, O.E. Franco3,4,5, S.W. Hayward3,4,5, D. Li2, D.J. Webb1,3
1Biological Sciences, Vanderbilt University, Nashville, TN, 2Mechanical Engineering, Vanderbilt University, Nashville, TN, 3Cancer Biology, Vanderbilt University, Nashville, TN, 4Urologic Surgery, Vanderbilt University, Nashville, TN, 5Surgery, NorthShore University HealthSystem, Evanston, IL

Contact author: Begum Erdogan
begum.erdogan@Vanderbilt.Edu
Lab (615) 343-9031

At ASCB 2015
Author presents:
Microsymposium 01: Cell Motility & Migration
Sunday, December 13
12:05-12:10 pm
Microsymposia Room 1

Integrins & Cell-ECM Interactions
Tuesday, December 15
1:30-3:00 pm
P2225
Board Number: B1356
ASCB Learning Center

For ASCB, contact: John Fleischman
jfleischman@ascb.org

Video available: "JHUcells on CAF-CDM" https://vimeo.com/147615483
Caption for video: Red labeled JHU12 head and neck carcinoma cells are migrating on CAF-derived extracellular matrix (green). Images were taken every 10 minutes for 3 hours using a confocal microscope.

John Fleischman | EurekAlert!

More articles from Life Sciences:

nachricht Newly designed molecule binds nitrogen
23.02.2018 | Julius-Maximilians-Universität Würzburg

nachricht Atomic Design by Water
23.02.2018 | Max-Planck-Institut für Eisenforschung GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Attoseconds break into atomic interior

A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.

In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...

Im Focus: Good vibrations feel the force

A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.

By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...

Im Focus: Developing reliable quantum computers

International research team makes important step on the path to solving certification problems

Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Basque researchers turn light upside down

23.02.2018 | Physics and Astronomy

Finnish research group discovers a new immune system regulator

23.02.2018 | Health and Medicine

Attoseconds break into atomic interior

23.02.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>