Local environmental conditions, such as oxygen supply, blood vessel supply, and mechanical stress control the size of cancerous tumors. Tumors experience mechanical stress as they expand into the surrounding tissue.
Tumors can overcome this obstacle to a certain extent, because they are stiffer than the surrounding tissue. However, mechanical stress eventually causes the cancer cells to die.
Perhaps if we more deeply understood the underlying molecular-level basis of how mechanical stress impacts cancer cells, we may partly understand why some people's cancer is more aggressive (malignant) than others. This may help in deriving treatments for cancer, and is a question that has been pursued by Lance Munn (Massachusetts General Hospital and Harvard Medical School) and coworkers.
Quantifying the effect of mechanical strength.
The scientists grew cancer cells in agarose gels. The purpose of the agarose gel was to keep the cancer cells in one place (prevent their random distribution throughout the gel), primitively simulating tumor growth in biological tissue.
Fluorescent micrometer-scale beads were added to the gel. Their purpose was to provide a means to quantify gel compression; more beads in a given volume means the gel is more compressed.
Thus, under fluorescent microscopy, the relationship between the size of the simulated tumor and the compression of the gel (mechanical stress) can be quantified. Measurements of cancer cell proliferation and cell death were achieved through standard protocols.
Simulated tumor growth and local mechanical strength.
The scientists found that cancer cell proliferation (simulated tumor growth) exerted significant pressure on the immediate surrounding gel (0.5% agarose) after 17 days of growth (at roughly 150 micrometer simulated tumor diameter). After 30 days, it had grown to roughly 250 micrometers in diameter, and exerted approximately 1.6 times the normal pressure on the gels.
This corresponds to a 37.5% increase in strain, approximately 4% of one atmosphere of pressure on the immediate surrounding gel. This stress sometimes caused the gel to crack, and allowed the simulated tumor to expand into the cracks without the impact of mechanical stress.
Effect of mechanical strength on cancer cell proliferation and death.
The scientists wanted to expand on these results to determine how the mechanical strength of the gel impacts cancer cell proliferation and "apoptosis" (programmed cell death, known as "cell suicide"). They found that cancer cells near the edge of the simulated tumor (region of greatest mechanical strength) exhibited lower growth rates than cells in regions of lower mechanical strength.
After twelve days, in 0.5% agarose gel, the cancer cells began to die by apoptosis. After approximately one month, cell death was extensive, and increased from there.
There was a positive linear relationship between cell death and local mechanical stress on the cells. All of this argues that mechanical stress eventually kills cancer cells; broadly similar results were also observed using other methods of imparting mechanical stress to cancer cells.
Using this information to treat cancer.
The scientists' most important goal was to begin to figure out the molecular-level basis of how mechanical stress kills cancer cells. This may help devise new treatments for cancer.
Inhibiting a specific known apoptosis ("cell suicide") pathway reduced cell death in response to mechanical strength. This may help scientists understand how to control aggressive strains of cancer; perhaps their apoptosis pathways are turned off.
This last hypothesis is currently speculative. However, it warrants further attention, as a unique compliment to the many different treatment options that are being developed for cancer.
for more information:
Cheng, G.; Tse, J.; Jain, R. K.; Munn, L.
Micro-environmental mechanical stress controls tumor spheroid size
and morphology by suppressing proliferation and inducing
apoptosis in cancer cells.
PLoS ONE 2009, 4, e4632.