Field of Science

Motility of Cancer Cells

ResearchBlogging.orgCancer is a disease of multicellular organisms. In order to become multicellular, a certain amount of control needs to be exerted over each individual cell, cells can no longer move around, grow, and divide when they want too. Instead they must obey signals from the surrounding environment (including their fellow cells) which tell them what to do. Cancer, like anarchy, is what happens when the control breaks down, and individual cells start growing and dividing regardless.

Uncontrolled growth leads to a neoplasm, a large mass of abnormal tissue. These can be benign, and merely exist in the body without causing too many problems, or they can start to become cancerous, invading surrounding tissues, and sometimes entering the bloodstream and spreading to further locations within the body.

(Because of this, cancer is primarily a disease of deterministic multicellular organisms. Plants and other non-determinists can get tumours, but tend not to be so badly affected by them, as they are constantly growing anyway)

In order to break away from the neoplasm and spread the disease cancer cells must gain motility. Studying how cancer cells move can be difficult in vivo because the conventional method of immuno-histology (which involves taking slices out of a tumour during development then fixing and staining them) prevent movement all together. Newer work has been done using Intravital imaging (shown diagrammatically on the rather cute little picture on the right) , where a fluorescently-labelled tumour is generated in an animal and then observed while the animal is anaesthetised. This gives a perfect in vivo image of what is actually happening inside the living tumour cell, in these images you can see cells moving in real time, and examine how they act under the effects of internal mutations and changes in external conditions.

One of the things that this type of imaging revealed was that most of the cells in a tumour don't move (less than 0.1% tumour cells in vivo/hour). Furthermore, there were two types of movement. Firstly, individual cells, that darted around on their own, fairly quickly and in all directions. Secondly large clumps of cells, that moved relatively slowly, but in the same direction with a more ordered internal microtubular structure.

Single celled movementTwo types of movement were first described; mesenchymal and amoeboid. As the main difference between them lies in the speed and number of direction changes it has been suggested that the distinction may be an artifact of different experimental conditions, rather than actual physical difference. The movement (which has been studied extensively in mesenchymal cells as they can be stuck down onto 2D surfaces) is initiated by signals to receptor tyrosine kinases. These turn on the small G-protein, Rac which, among other things, activates Arp2/3 proteins, which control the nucleation of actin subunits. In the diagram above the actin is shown in red, and it is used to generate movement of the cell. As the cell is forcing it's way through a thick external extracellular matrix (EMC) it also secretes proteases and MMPs to break this down, allowing easier forward movement.

Collective cell movement
(All images are taken from the reference below, and I've included the key for those with an interest in how eukaryote cells hold themselves together)

Collective motility is the movement of whole groups of cells, either in clusters or chains. These cells can move between tissues, spreading the tumour (in particular they can get into the lymph system) but they are not normally found in the bloodstream. Interestingly, collective motility is seen when the conditions for single-cell motility have been blocked, suggesting that the rapid-moving single cells are a transient stage in order to get the tumour into the bloodstream. Once it finds a new environment, it reverts back to the less-motile stage, with large clumps of tissue still able to (very slowly) manoeuvre themselves into nearby tissues.

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SAHAI, E. (2005). Mechanisms of cancer cell invasion Current Opinion in Genetics & Development, 15 (1), 87-96 DOI: 10.1016/j.gde.2004.12.002

5 comments:

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Alejandro Montenegro-Montero said...

This just out: Giampieri, S. et al. Localized and reversible TGFbeta signalling switches breast cancer cells from cohesive to single cell motility. Nature Cell Biology. 11, 1287–1296 (2009)

http://dx.doi.org/10.1038/ncb1973

Captain Skellett said...

My friend always describes cancer as like a moshpit - everyone crammed in together and no organisation at all!

I've never thought about plants having cancer. What happens to them?

Lab Rat said...

I'm not sure if it technically defines as 'cancer' but plants can certainly get tumours, usually in response to the action of a pathogen or a pest.

There's some (vaguelly confusing) information here: http://www.wikigenes.org/e/mesh/e/8063.html which has plenty of references if you want to read up on any of them.

disa said...

I love it ! Very creative ! That's actually really cool Thanks.