Mechanical Stress May Induce Formation of Cancer Cells

Researchers have developed a novel technique for studying the forces that induce mistakes in chromosome distribution that have the potential to initiate growth of cancer cells.

In order to study mechanical effects that influence the outcome of cell division, investigators at the University of California, Los Angeles (USA) developed a novel microfluidic perfusion-culture system that allowed controllable variation in the level of cell confinement in a single axis allowing observation of cell growth and division at the single-cell level.

This novel culture platform allowed for both alterations in the geometry of the microenvironment, specifically the space in which the cell was allowed to grow and divide, as well as the elasticity of the substrate on which the cell was dividing. By using the microfluidic device to compress the cells, the investigators minimized cell death due to lack of nutrients, as media was constantly perfused through the compression chamber. The device also allowed for facile imaging of cells, as they were in a single focal plane.

The investigators used this tool to study growth and division of single HeLa (human cervical carcinoma) cells. They reported in the June 25, 2012, online edition of the journal PLoS ONE that mechanically confined cell cycles resulted in stressed cell divisions that manifested as: (i) delayed mitosis, (ii) multidaughter mitosis events (from three up to five daughter cells), (iii) unevenly sized daughter cells, and (iv) induction of cell death. In the highest confined conditions, the frequency of divisions producing more than two progeny was increased 50-fold from unconfined environments, representing about one-half of all successful mitotic events. Most daughter cells resulting from multipolar divisions were viable after cytokinesis and were in some cases observed to re-fuse with neighboring cells post-cytokinesis.

“We hope that this platform will allow us to better understand how the 3-D mechanical environment may play a role in the progression of a benign tumor into a malignant tumor that kills," said senior author Dr. Dino Di Carlo, associate professor of bioengineering at the University of California, Los Angeles. “Even though cancer can arise from a set of precise mutations, the majority of malignant tumors possess aneuploid cells, and the reason for this is still an open question. Our new microfluidic platform offers a more reliable way for researchers to study how the unique tumor environment may contribute to aneuploidy.”

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