Does an increase in cancer cell traction forces increase metastasis of the cancer cells?

Question

I am not very familiar with biology, but I have read some articles about cell traction forces lately, where the cells are cancer cells. I found this very interesting, so I thought it might be nice to read about the relationship between cell traction forces and metastasis for cancer cells. I thought that an increase in cancer cell traction force should indicate that there would be more metastasis. I have looked at two references, but one of the articles says that increasing the cell traction force increases metastasis [[Kraning-Rush et al. (2012)](https://www.researchgate.net/publication/221887424_Cellular_Traction_Stresses_Increase_with_Increasing_Metastatic_Potential)], while the other says the opposite [[Indra et al. (2011)](https://www.researchgate.net/publication/49817265_An_in_vitro_correlation_of_mechanical_forces_and_metastatic_capacity)]. Both are experimental articles.My question is therefore:Is it correct that most often, an increase in cancer cell traction forces would increase metastasis, or should it most often decrease metastasis?

Answer 1

There are a variety of effects traction has on metastatic cancer cells. One caveat to remember. Cancer cell is not an unique entity. There around 500 cancers, and there metastatic cells may behave similarly, but may behave in their own special way (i.e secondary tumor location targeting).

The other thing to realize (and I used to do this type of research so i have no issue admitting its shortcomings) is that most of the papers you will com across analyze the cell i 2D (i.e. in a dish). That is a very foreign environment to the 3d world they exist in in the body/tumor.

Now, after all of those caveats allow me to answer your question (sort of). Cell adhesions are the feet that metastatic type cells uses to move along a substrate. In metastatic cells (again, depending upon which one we're talking about, certain adhesion proteins are increased in either expression level or activity. While, at the same time (often in the same cell) other adhesion proteins (which don't normally act in opposition to the hyperactivated proteins) are found to be decrease in either expression or activity.

The bottom line is that this is an on going area of research (if you minimize metastasis, you can skyrocket survivability rates. The issue is to affect the proteins in the cancer cells and not normal cells (where almost all of these proteins are also expressed. You don't want to light a candle in one room for light and burn down the entire house.

Hope this helped, feel free to contact.

Cheers,

drsjp

Answer 2

A couple quick definitions before we start. Metastasis is the migration of a tumour or cancer from one location to another in the body and cancer is a cell that divides uncontrollably leading to tumour development. The major causes; include accumulated mutations (from lifestyle) and genetic pre-disposion  (BRCA 1, 2). Now on to malignancy, once a cell has become cancerous it can regress to a type of cell called a mesenchymal stem cell.  

Mesenchymal cells are different than typical cells. They divide, a lot and they are mobile. Mesenchymal cells are important during normal development. Where their mobility allows organisms to develop limbs, organs and blood vessels. Mesenchymal cells can move because they have less rigid (more bloblike) cell membranes and they have less interest in attaching to nearby cells. This makes sense if we need to get a cell from the hip to the toe or if we need to get a cell from the stomach to the colon. This only happens during development so think in womb and during stages such as puberty. When an cancer cell becomes Mesenchymal it gains that same ability to move that developmental mesenchymal cells had.

Essentially, when the cancer cell switches to mesenchymal it becomes a hitchhiker. Instead of staying in the tumour interacting with other cancer cells, it prefers to interact with the Matrix (the highway system) of the tissue. When the de-differentiated cancer cell (aka mesenchymal cancer cell) hitchhikes to a blood or lymph vessel, that mesenchymal cancer cell can move and set up shop in another organ or tissue. With that hitchhiking we have the development of two tumours each located in different parts of the body.  

I hope this helped,

AK

P.S. If you have follow up questions let me know.