Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Sea squirt cells shed light on cancer development

27.07.2011
Specialized structures used by cancer cells to invade tissues could also help them escape protection mechanisms aimed at eliminating them, a UA-led research team has discovered

Delicate, threadlike protrusions used by cancer cells when they invade other tissues in the body could also help them escape control mechanisms supposed to eliminate them, a research group led by led by Bradley Davidson in the University of Arizona's department of molecular and cellular biology reports in Nature Cell Biology.

Studying embryos of the sea squirt Ciona intestinalis, the researchers discovered that even non-invasive cells make the delicate, highly transient structures known as invadopodia. The group found that future heart cells in the Ciona embryo use invadopodia to pick up chemical signals from their surroundings. These so-called growth factors provide the cells with clues as to where they are in the developing embryo and what type of cell they are supposed to turn into.

The results suggest that this previously unknown role of invadopodia could also be at play in the case of cancer cells: Their invadopodia may serve to bind similar signaling molecules that protect them from the body's elimination processes, thereby ensuring their survival.

"These are special invasive protrusions and they are seen only in rare cell types and cancer cells. We are the first to see them in the developing Ciona embryo, and we certainly didn't expect to see them in that context," said Davidson, who is a member of UA's Arizona Cancer Center. "In Ciona, the cells that are making these special kinds of arms do not use them for invasion. Those cells behave very differently from cancer cells."

Cells form invadopodia in a process that resembles pitching a tent: They push a portion of their rigid, internal scaffolding into a portion of the cell membrane which envelopes the entire cell, thereby extending a long, thin protrusion outward.

"These structures are extremely fragile. The cells grow and retract them over short periods of time," Davidson said. "For that reason, they are almost impossible to see in fixed specimens. We think they are probably a lot more common than people realize."

Cancer cells have been known for a long time to use invadopodia to break through tissues that serve as natural barriers keeping cells in check and make sure they stay in their assigned locations.

"Most cells can never cross those epithelial barriers," Davidson said. "They play an important role in controlling the location and movement of cells, especially in a developing embryo."

"When a tumor spreads, its cells have to break out and escape to other tissues," Davidson explained. "To do that, they have to invade a blood vessel, travel to their new location and then get back out, which requires them to squeeze through the linings of blood vessels and invade similar barriers at their destination."

Because of the cancer cells' ability to break through barriers and invade tissues, researchers are very interested in the mechanisms allowing those cells to behave this way.

"There are a number of ways they can break through the barriers," Davidson explained. "Sometimes they'll actually fully disrupt the wall, make a break in the wall and push through. Cancer cell invadopodia secrete proteins that help make these breaks and also can physically push cells aside."

The cells in Ciona, however, use their invadopodia quite differently, the researchers discovered.

Inititally, the team was investigating a completely different scientific question: how the heart forms in the developing Ciona embryo. The sea squirt's simple body structure belies its close biological kinship to vertebrates, including humans.

In fact, Ciona shares most of its genes with vertebrates. Ciona has a brain, eyes, a mouth and a gut and a heart. While fundamentally similar, the developing Ciona embryo is much less complex than a vertebrate embryo. The combination of genetic similarity and anatomical simplicity makes the sea squirt an ideal model organism to disentangle biological processes that would be too complex to study in vertebrates.

Davidson is especially interested in figuring out the genes controlling heart development, with the goal of deciphering the underlying mechanisms of congenital heart defects in humans. Unlike its human counterpart, Ciona's heart is very simple and develops in a very specific and predictable process. One particular cell gives rise to all future heart cells. When that cell undergoes its first division resulting in two daughter cells, only one of them, and always the same one, becomes a heart progenitor cell continuing the lineage while the other gives rise to tail musculature.

"We were trying to figure out how the cells make that decision," Davidson said. "We knew that there are chemical signals, growth factors, that coax one of the cells into becoming a heart cell, but we had no idea why one cell responds to those signals and the other one doesn't."

When the researchers labeled the membranes of the cells to make them visible with a highly sensitive laser microscope, they discovered that the heart progenitor cell differed from its sister in that it made invadopodia. Unlike cancer cells, however, the cells in Ciona did not appear to use their invadopodia to invade tissues.

"They engulf an adjacent cell, but then pull back," Davidson said. "They never do anything else with their invadopodia, they never push through. That's what made us ask, why are they doing this?' It suggests they use their protrusions for something else."

The researchers then discovered that the cells making invadopodia responded much stronger to growth factor signaling than other cells, suggesting their invadopodia function as antennae to pick up signals that instruct the cell to become a heart progenitor cell.

This finding offers an intriguing possibility: Could it be that cancer cells too use their invadopodia as antennae, giving them the additional benefit of being more receptive to, or even independent of, growth factor signaling?

When cells become cancerous, they take on a dangerous life of their own. For example, a normal cell will not proliferate unless it is being told to do so by chemical signals such as growth factors. Likewise, a cell that is part of a tissue will stay in its assigned place.

Protective mechanisms are in place to prevent cells from going rogue. Most mutations that could make a cell cancerous trigger a genetic auto-destruction program. Cancer develops if a cell manages to accumulate cancerous mutations enabling it to wrestle itself free from such control mechanisms and proliferates even in the absence of growth factors or leaves its home tissue and invades other tissues.

"Our findings in Ciona may change the way we think about cancer," Davidson said. "Instead of starting out as a mass of cancer cells – the tumor – it is possible that small groups of cells or even single cells gain the ability to metastasize very early on by using invadopodia to boost their survival signaling."

"Such a cancer progenitor cell would be very difficult to detect because there is no tumor yet. There are likely specific proteins or specific components that allow a cell to use its invasion as an antenna. If we can find those components, they could be promising targets for cancer therapy because this is a process that most cells would never need to do. It's very specific to a cancer cell. So the hope would be to target those cells very early, before they start making tumors, without harming the rest of the cells."

Time-lapse movies of invadopodia:

This movie shows a cell pushing out and retracting two invadopodia over the course of less than 30 minutes: http://www.nature.com/ncb/journal/vaop/ncurrent/extref/ncb2291-s5.mov

A 3-D rotating view showing two cells with invadopodia. One of the cells completely engulfed another with its invadopodia, forming what looks like a box: http://www.nature.com/ncb/journal/vaop/ncurrent/extref/ncb2291-s2.mov

Caught in the act: In this Ciona embryo, a cell (labeled green) can be seen pushing invadopodia into the inside of the embryo's epidermis, only to retract them about 20 minutes later: http://www.nature.com/ncb/journal/vaop/ncurrent/extref/ncb2291-s6.mov

Credit for all videos: Davidson Lab

Daniel Stolte | EurekAlert!
Further information:
http://www.arizona.edu

More articles from Life Sciences:

nachricht Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Water - as the underlying driver of the Earth’s carbon cycle

17.01.2017 | Earth Sciences

Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

17.01.2017 | Materials Sciences

Smart homes will “LISTEN” to your voice

17.01.2017 | Architecture and Construction

VideoLinks
B2B-VideoLinks
More VideoLinks >>>