Cancer cells use body's wound-healing mechanism to spread

February 10, 2014 by Mohit Kumar Jolly, The Conversation

Metastasis, the spread of cancer cells from a primary tumour to different organs, is responsible for more than 90% of deaths due to cancer. Current treatments such as chemotherapy or radiotherapy are effective against primary tumours, but they cannot stop or kill the circulating cancer cells in the bloodstream. This means that understanding how cancer cells start to metastasise is crucial for developing new anti-metastasis therapies.

Now, researchers at Rice University (including myself) have deciphered how a network of genes allows to "decide" when to metastasise, thus opening up new therapeutic avenues.

Cancer cells in a primary tumour are usually fixed and immovable (sessile). However, if some of the cancer cells from the primary tumour start to invade neighbouring healthy tissue and enter the bloodstream to spread to different organs, it is bad news for the patient, because each one of these circulating cancer cells is capable of giving rise to a new tumour elsewhere in the body. Every cancer cell in the primary tumour either stays bound to its neighbours or metastasises. This decision is taken by a network of genes that functions as a switch, allowing each cell to either be "on" (migrating) or "off" (not migrating).

We discovered that this genetic switch also allows for a third choice that lies somewhere between "on" and "off": cancer cells can move collectively, or migrate while still bound to their neighbours. These findings are crucial, because they underline a striking similarity in the collective cell migration of cancer cells and the kind of cell migration seen during wound healing.

This means that anti-metastasis strategies must be developed while keeping in mind that they do not inhibit wound healing. Even more care should be taken as the wound-healing drugs should not promote metastasis, in case a tumour is present.

Switch to spread

After circulating, cancer cells exit the bloodstream to settle at a distant organ. They switch back to being sessile and start growing another tumour at that organ. We show that moving collectively is advantageous to the cancer cells, because it is much easier for collectively moving cells rather than individually moving cells to switch back to a sessile state at a distant organ and start growing another tumour.

The metastasis "decision switch" consists of two specialised pairs of proteins, namely (SNAIL and microRNA34) and (ZEB and microRNA200). Both pairs are "mutually inhibitory", with each partner in a pair inhibiting the production of the other. Imagine two people, A and B, who hate each other and refuse to attend a party where the other is present. Therefore, usually, in such pairs, one gets only two possibilities: either only A attends or only B attends – the concentration of the first protein is high and the second low, or vice-versa. In sessile cancer cells, the concentration of microRNAs is higher and that of ZEB and SNAIL low, and vice-versa for individually migrating cells.

The simple explanation then would be that these mutually inhibitory pairs behave as a switch, allowing for an "on" and an "off" state. However, our study shows that they actually behave as two switches, allowing for three possibilities. This they do because depending on the strength of inhibition (or degree of hatred) and other regulations (such as self-activation), such pairs can behave differently from being a usual two-way switch.

SNAIL and microRNA34 inhibit each other weakly. As a result, they both can be present at the same time (without driving any of them to extinction), with their exact amounts being decided by interactions with other genes – allowing three cases – A present, B absent; B present, A absent; and both A and B present under certain conditions.

It is the dance of these two pairs of proteins which allows cancer cells to have a three-way switch, rather than the previously thought two-way switch. Since this decision-making switch is common across cancers that originate in breast, prostate, colon, or pancreas, the results are potentially of importance for more than 60% of all cancer patients.

This process is remarkably similar to the body's repair mechanism, where group of skin cells move to close a surface wound. Their collective movement allows the wound to be healed. Using this strategy often means they gain the best of both worlds – cell-cell cooperation to spread and uncontrolled growth. Knowing this process can enable us to better tackle , one of the most critical areas of cancer research and future treatment.

Explore further: Physicists decode decision circuit of cancer metastasis

Related Stories

Physicists decode decision circuit of cancer metastasis

October 24, 2013
Cancer researchers from Rice University have deciphered the operating principles of a genetic switch that cancer cells use to decide when to metastasize and invade other parts of the body. The study found that the on-off ...

New breast cancer stem cell findings explain how cancer spreads

January 14, 2014
Breast cancer stem cells exist in two different states and each state plays a role in how cancer spreads, according to an international collaboration of researchers. Their finding sheds new light on the process that makes ...

New prostate cancer drugs may not be targeting root cause of disease, scientists warn

January 27, 2014
(Medical Xpress)—New drugs being developed for the treatment of prostate cancer may not be targeting the root cause of the disease, according to research published today (Friday, 24 January 2014) in Cell Death & Differentiation.

Research discovers non–toxic cancer treatment

January 23, 2014
(Medical Xpress)—A University of Queensland researcher is developing a "Trojan horse" non-toxic treatment for human breast cancer.

Researchers discover protein that may control the spread of cancer

February 26, 2013
Researchers at the University of Hawai'i Cancer Center have uncovered a novel mechanism that may lead to more selective ways to stop cancer cells from spreading. Associate Professor Joe W. Ramos PhD, a cancer biologist at ...

New study shows insight into breast cancer cell migration

October 29, 2013
(Medical Xpress)—A new study by University of Kentucky Markey Cancer Center researchers Min Chen and Kathleen O'Connor shows that a specific protein may assist breast cancer cells in metastasizing.

Recommended for you

Researchers discover novel mechanism linking changes in mitochondria to cancer cell death

February 20, 2018
To stop the spread of cancer, cancer cells must die. Unfortunately, many types of cancer cells seem to use innate mechanisms that block cancer cell death, therefore allowing the cancer to metastasize. While seeking to further ...

Stem cell vaccine immunizes lab mice against multiple cancers

February 15, 2018
Stanford University researchers report that injecting mice with inactivated induced pluripotent stem cells (iPSCs) launched a strong immune response against breast, lung, and skin cancers. The vaccine also prevented relapses ...

Induced pluripotent stem cells could serve as cancer vaccine, researchers say

February 15, 2018
Induced pluripotent stem cells, or iPS cells, are a keystone of regenerative medicine. Outside the body, they can be coaxed to become many different types of cells and tissues that can help repair damage due to trauma or ...

Team paves the way to the use of immunotherapy to treat aggressive colon tumors

February 15, 2018
In a short space of time, immunotherapy against cancer cells has become a powerful approach to treat cancers such as melanoma and lung cancer. However, to date, most colon tumours appeared to be unresponsive to this kind ...

Can our genes help predict how women respond to ovarian cancer treatment?

February 15, 2018
Research has identified gene variants that play a significant role in how women with ovarian cancer process chemotherapy.

First comparison of common breast cancer tests finds varied accuracy of predictions

February 15, 2018
Commercially-available prognostic breast cancer tests show significant variation in their abilities to predict disease recurrence, according to a study led by Queen Mary University of London of nearly 800 postmenopausal women.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.