Tumor-Causing Cells Are Squishier
A new tool developed by a team of scientists at The Methodist Hospital Research Institute Physical Sciences-Oncology Center (Methodist PS-OC) separates tumor-causing cancer cells from more benign cells by sifting the cells through an ordered set of microscopic posts. As reported in the Proceedings of the National Academy of Sciences, only more flexible, tumor-causing cells can navigate the micrometer-sized spaces between posts on a device that the researchers have named the MS-Chip. “The throughput of an MS-Chip is at the level of one million cells,” said Lidong Qin, who led the research team. “When a stiff cell blocks one particular barrier, many other bypasses will allow flexible cells to flow through.”
This work supports the hypothesis that cell squishiness correlates with tumor-producing potential of cells. Most normal cells contain a developed cytoskeleton, a scaffolding network of tiny but strong rod-shaped proteins that give cells their shape and structure. In their drive to divide, cancer cells may be diverting resources away from developing a cytoskeleton in favor of division, hence the squishiness.
The team of scientists showed that flexible cells separated by the MS-Chip exhibited gene expression patterns consistent with cancer stem cells. Subsequent analysis of separated cells showed the flexible cells were less likely to express cell cytoskeleton genes and more likely to express the motility genes that could contribute to metastasis.
A growing awareness of cancer stem cells' role in cancer metastasis and recurrence and has been frustrated by the absence of technology that makes this knowledge useful to doctors and their patients. Up to now, there has been no way of quickly and reliably separating and identifying the more dangerous tumor-causing cells from a biopsy. “Our microfluidics cell separation via MS-Chip provides a high throughput method that can particularly sort cells to different levels of stiffness, which opens a new avenue to study stiffness related cellular and molecular biology,” Dr. Qin said.
Currently, each MS-Chip costs about $10 to produce, but the investigators project that when mass produced, the device would cost about $1 apiece. According to Dr. Qin, that would make running a mechanical cell separation even less expensive than flow cytometry cell sorting, the current standard technique to separate different types of cells.
While Dr. Qin’s team studied breast cancer cells, a study from Georgia Institute of Technology investigators, the results of which were published in the journal PLoS One, suggests that this device could be useful for detecting other types of cancer cells, too. A team led by Todd Sulchek found that highly metastatic ovarian cancer cells are several times softer than less metastatic ovarian cancer cells. Dr. Sulchek and his team used atomic force microscopy to measure differences in cell stiffness between normal and highly metastatic ovarian cancer cells.
Dr. Qin and his colleague’s work, which is detailed in a paper titled, “Microfluidics separation reveals the stem-cell-like deformability of tumor-initiating cells,” was supported in part by a Methodist PS-OC Pilot Project grant from the National Cancer Institute's Physical Sciences in Oncology initiative, a program that aims to foster the development of innovative ideas and new fields of study based on knowledge of the biological and physical laws and principles that define both normal and tumor systems. Investigators from the University of Texas MD Anderson Cancer Center also participated in this study. An abstract of this paper is available at the journal's Web site.
The research from Dr. Sulchek’s group appears in a paper titled “Cell Stiffness Is a Biomarker of the Metastatic Potential of Ovarian Cancer Cells.” This paper is available free-of-charge from the journal’s Web site.