A different view of cancer cells: New study measures physical changes in tumor cells as they become metastatic

April 23, 2013 by Anne Trafton
By measuring the speed at which a cell enters a narrow constriction, MIT engineers can determine how deformable the cell is. Credit: SANGWON BYUN AND JOSEPHINE SHAW

Most cancer deaths are caused by metastatic tumors, which break free from the original cancer site and spread throughout the body. For that to happen, cancer cells must undergo many genetic and physical changes.

Many of those have been studied extensively, but it has been more difficult to study the physical changes. Now, MIT researchers have developed a way to study three key physical properties of cancer —their mass, and —on a large scale.

Using this system, the researchers have analyzed how changes in those traits may allow cancer cells to migrate to new sites: Scientists have previously observed that cell lines with higher metastatic potential are generally more deformable, but the MIT team found that decreased friction also appears to help cancer cells traverse , suggesting that friction may play a role in the ability of cancer cells to travel in and reach new tumor sites.

"Our measurements provide an additional perspective on cell properties that may complement genomic and proteomic approaches," says Sangwon Byun, an MIT postdoc and lead author of a paper describing the findings in the Proceedings of the National Academy of Sciences the week of April 22.

The system that Byun and colleagues used to study the cancer cells is based on a device previously developed by Scott Manalis, a member of MIT's Koch Institute for Integrative and an MIT professor of . Manalis, the senior author of the PNAS paper, has previously demonstrated that this system, known as a suspended microchannel resonator (SMR), can very accurately measure the mass and density of individual cells.

Inside the SMR, cells flow through a channel carved into a tiny slab that vibrates at a that can be measured with a . As each cell flows through the channel, the slab's resonant frequency changes, allowing the researchers to calculate the cell's mass and density.

Putting the squeeze on cells

For the new study, the researchers modified the system so they can also track each cell's velocity as it passes through a narrow constriction in the channel. This allows them to estimate both the cell's deformability and how much friction it experiences as it travels through the constriction, which is slightly smaller than the diameter of the cells under study. Cells that squeeze through this opening faster are more deformable.

In one set of experiments, the researchers compared the deformability of two types of mouse lung-cancer cells. The two cell types differ in the expression of only one transcription factor, known as NKX2-1: Cancer cells not expressing this factor are more aggressive and likely to metastasize. The researchers found that cells that do not express NKX2-1 entered the narrow channel more rapidly, confirming previous studies showing that are more deformable.

The researchers then compared nonmetastatic and metastatic cells from the same mouse model, and found that these metastatic cells were not only more deformable, but they also traveled faster through the length of the constriction (about 50 microns). A similar observation was made when comparing nonmetastatic to metastatic human lung-cancer cell lines. "It seems that the cells experience less friction, making it easier for them to get through the channels," Byun says.

This phenomenon has not been seen before, in part because scientists haven't had a good way to simultaneously define the size, deformability and friction of individual flowing cells. Many factors could influence the friction between the cell and the channel wall, including changes in cell-surface expression. For example, metastatic cancer cells often have an increased amount of sialic acid molecules on their surfaces, which may alter friction, the researchers say.

The new MIT system is "probably the world's most sensitive instrument for measuring a number of different biophysical properties of individual cells," says Mehmet Toner, a professor of biomedical engineering at Massachusetts General Hospital and Harvard Medical School who was not part of the research team. "It's very important to know whether metastatic cells have biophysical properties different than normal or nonmetastatic cancer cells, allowing them to go through narrow spaces."

Circulating tumor cells

The researchers are now using their system to detect circulating tumor cells (CTCs) in cancer patients' blood samples. The current approach to finding CTCs, which can range in number from a few to several thousand per milliliter of blood, is by looking for a marker (a molecule found on a cell's surface) that is preferentially expressed by epithelial cells. However, that approach may miss CTCs that don't express the chosen epithelial markers.

"When you use a specific marker to look for these cells, you find the cells that you're looking for, but you may be missing a whole population of cells," says Josephine Shaw, an MIT graduate student and a co-author of the paper. "It's possible that by using a more holistic and physical approach, we may be able to find certain cells that we wouldn't be able to find molecularly, because we wouldn't be able to guess ahead of time what these cells would be expressing."

Once those cells were captured, scientists could do many more types of tests on them, including analysis of genes expressed and proteins produced, to learn more about how they break free from tumors.

The researchers also plan to study physical changes that occur in cells as they go through the epithelial-mesenchymal transition—a process that allows to lose their adhesion and become mobile, helping them metastasize.

Explore further: Squeezing ovarian cancer cells to predict metastatic potential

Related Stories

Squeezing ovarian cancer cells to predict metastatic potential

October 10, 2012
(Medical Xpress)—New Georgia Tech research shows that cell stiffness could be a valuable clue for doctors as they search for and treat cancerous cells before they're able to spread. The findings, which are published in ...

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 ...

Biologists pinpoint a genetic change that helps tumors move to other parts of the body

April 6, 2011
MIT cancer biologists have identified a genetic change that makes lung tumors more likely to spread to other parts of the body. The findings, to be published in the April 6 online issue of Nature, offers new insight into ...

Transition in cell type parallels treatment response, disease progression in breast cancer

January 31, 2013
A process that normally occurs in developing embryos – the changing of one basic cell type into another – has also been suspected of playing a role in cancer metastasis. Now a study from Massachusetts General Hospital ...

Signature of circulating breast tumor cells that spread to the brain found

April 10, 2013
Some breast tumor circulating cells in the bloodstream are marked by a constellation of biomarkers that identify them as those destined to seed the brain with a deadly spread of cancer, said researchers led by those at Baylor ...

Recommended for you

Cancer vaccines need to target T cells that can persist in the long fight against cancer

September 25, 2017
Cancer vaccines may need to better target T cells that can hold up to the long fight against cancer, scientists report.

MRI contrast agent locates and distinguishes aggressive from slow-growing breast cancer

September 25, 2017
A new magnetic resonance imaging (MRI) contrast agent being tested by researchers at Case Western Reserve University not only pinpoints breast cancers at early stages but differentiates between aggressive and slow-growing ...

Lung cancer treatment could be having negative health effect on hearts

September 25, 2017
Radiotherapy treatment for lung cancer could have a negative effect on the health of your heart new research has found.

Alternative splicing, an important mechanism for cancer

September 22, 2017
Cancer, which is one of the leading causes of death worldwide, arises from the disruption of essential mechanisms of the normal cell life cycle, such as replication control, DNA repair and cell death. Thanks to the advances ...

'Labyrinth' chip could help monitor aggressive cancer stem cells

September 21, 2017
Inspired by the Labyrinth of Greek mythology, a new chip etched with fluid channels sends blood samples through a hydrodynamic maze to separate out rare circulating cancer cells into a relatively clean stream for analysis. ...

Whole food diet may help prevent colon cancer, other chronic conditions

September 21, 2017
A diet that includes plenty of colorful vegetables and fruits may contain compounds that can stop colon cancer and inflammatory bowel diseases in pigs, according to an international team of researchers. Understanding how ...

0 comments

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.